Technical Abstract: Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol are risk factors for cardiovascular disease and blood triglycerides reflect key metabolic processes including sensitivity to insulin. Blood lipoprotein and lipid concentrations are heritable. To date, the identification of causal genes for Mendelian dyslipidemic syndromes has transformed our understanding of lipoprotein metabolism and the treatment of cardiovascular disease. Nonetheless, most of the heritability of blood lipoproteins and lipids remains unexplained by known genes and gene variants. Using genome-wide association data from three studies (n=8816) and targeted replication association analyses in up to 18,554 independent participants, we show that common single nucleotide polymorphisms (SNPs) at six new loci are reproducibly associated with LDL cholesterol, HDL cholesterol, and/or triglycerides (P<5x10-8 for each new locus). Of the six novel chromosomal regions, two were associated with a single lipoprotein or lipid trait: 1p13 (near CELSR2/PSRC1/SORT1) with LDL cholesterol and 1p31 (near ANGPTL3) with triglycerides. Three loci were related to two lipoprotein or lipid traits: 19p13 (near CILP2/PBX4) with LDL cholesterol and triglycerides and both 1q42 (in GALNT2) and 7q11 (near TBL2/MLXIPL) with HDL cholesterol and triglycerides. One locus, 8q24 (near TRIB1), affected all three lipoprotein or lipid traits. At 1p13, the LDL-associated SNP was also strongly correlated with liver transcript levels of SORT1 (P=2x10-26) as well as two other neighboring genes, suggesting that this SNP may act as a regional regulator of gene expression. Common polymorphisms at six novel loci have distinct effects on lipoprotein and lipid concentrations; understanding their molecular, cellular, and clinical consequences may inform therapy and clinical care.