Inclusion Criteria:

• Patients must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. Note: It is acceptable to have additional signatures if required by local regulations
• Meet diagnostic criteria for schizophrenia according to DSM-IV (disorganized type [295.10], catatonic type [295.20], paranoid type [295.30], residual type [295.60], or undifferentiated type [295.90]) for at least 1 year before screening. Prior medical records, written documentation, or verbal information obtained from previous psychiatric providers obtained by the investigator must be consistent with the diagnosis of schizophrenia
• A total PANSS score between 60 and 120, inclusive, at screening and baseline
• Body mass index (BMI) of ³17.0 kg/m²
• Female patients must be postmenopausal for at least 2 years, surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before study entry and throughout the study. Effective methods of birth control include contraceptive pills, coil, depot injection of gestagen, subdermal implantation, hormonal vaginal ring, and transdermal depot patches. Women of childbearing potential must have a negative urine beta human chorionic gonadotropin (b HCG) pregnancy test result at screening
• Be capable of self-administering study medication (applies to oral supplementation) or have assistance with study medication administration consistently available throughout the first 4 weeks of the study

Exclusion Criteria:

• Unable to provide their own consent or involuntarily committed to psychiatric hospitalization
• A primary, active DSM-IV diagnosis on Axis I other than schizophrenia
• A decrease of ³25% in the total PANSS score between screening and baseline as calculated using the table provided by the sponsor (see attachment 12)
• Patients who have previously participated in this study
• A DSM-IV diagnosis of active substance dependence within 3 months before screening (nicotine and caffeine are not exclusionary)
• History of treatment resistance as defined by failure to respond to 2 adequate treatments with different antipsychotic medications (an adequate treatment is defined as a minimum of 6 weeks at maximum tolerated dosage)
• Relevant history or current presence of any significant or unstable cardiovascular, respiratory, neurological (including seizures or significant cerebrovascular disease), renal, hepatic, hematologic, endocrine, immunologic, morbid obesity (BMI>40 kg/m2) or other systemic disease
• History of any severe preexisting gastrointestinal narrowing (pathologic or iatrogenic) or inability to swallow oral study medication whole with the aid of water (applies to those subjects requiring oral tolerability only)
• Serum chemistry, hematology, or urinalysis results that are not within the laboratory's normal reference range and are deemed to be clinically significant by the investigator
• History or evidence of clinically significant hepatic disease [including aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 times the upper limit of normal] at screening
• History of neuroleptic malignant syndrome (NMS)
• Significant risk of suicidal or violent behavior, as clinically assessed by the investigator
• History of life-threatening allergic reaction to any drug
• Known or suspected hypersensitivity or intolerance to risperidone, paliperidone, 20% Intralipid, or any of their excipients (e.g., soybean oil, egg yolks, phospholipids, and glycerol)
• Have received an experimental drug or experimental biologic, or used an experimental medical device within 6 months before screening
• History of any active malignancy within the previous 5 years, with the exception of basal cell carcinomas
• Female patient who is pregnant or breast-feeding or is planning to become pregnant during the study
• Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator
• Patients who have participated in 2 or more clinical trials in the past year or in 1 clinical trial in the past 6 months (non-intervention, observational, and retrospective studies excluded)
• History of disallowed therapies: A typical injectable antipsychotic within 1 injection interval before screening. Use of clozapine in the 3 months prior to baseline. Risperidone LAI injection within 6 weeks before screening. A previous injection of paliperidone palmitate within 10 months before baseline. Electroconvulsive therapy (ECT) with 60 days before screening. Nonselective/irreversible MAOI antidepressants within 30 days before screening. Other antidepressants unless at a stable dosage for 30 days before screening or, unless the antidepressant is not necessary, and can be washed out by the baseline visit. Mood stabilizers, including lithium and all anticonvulsants, are not allowed during the double-blind treatment period, and must be washed out by Day -1. Antiparkinsonian medication should be washed out by Day -1. Beta-blockers must be washed out by Day -1. Other prescription, OTC, or herbal agents with psychoactive properties are not allowed during the double-blind treatment period, and must be washed out by Day -1. (Note on washed out:The duration of the washout is up to the discretion of the investigator but, in general, should be 5 times the elimination half-life)
• History or presence of circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, includingHeart Rate < 50 beats per minute,Demonstration of repeated prolonged QTc Fridericia interval > 450 msec, as measured on more than one ECG: The following cardiac conditions: sick sinus syndrome, complete AV block, congestive heart failure, polymorphic ventricular tachycardia. Clinically relevant hypocalcemia, hypokalemia or hypomagnesemia
• Concomitant use of drugs that prolong the QTc interval. Presence of congenital prolongation of the QT interval (Romano-Ward, Jervell and Lange-Niels syndrome