A retrospective pharmacogenetic (PGx) analysis was conducted, to evaluate the effect of functional genetic variants in the transporter OATP1B1 on the plasma pharmacokinetics (PK) of grazoprevir (GZR) and efficacy of elbasvir/grazoprevir (EBR/GZR) (Zepatier) treatment. Because GZR is an OATP1B1 substrate, three OATP1B1 (SLCO1B1) single nucleotide polymorphism (SNP) variants (rs4149056, rs2306283 and rs11045819) were examined. These three SNPs have previously been shown to be associated with changes in the pharmacokinetics of OATP1B1 substrates. A total of 1578 subjects from 10 Phase II and III clinical trials were included in this analysis. Genetic data was generated from DNA collected routinely from clinical study participants. For the PK-genetic analysis, linear fixed effect models were performed on the natural log transformed individual GZR PK parameter values. For the efficacy-genetic analysis, Firth penalized logistic regression models were performed on individual SVR12 values (a binary endpoint of SVR12 achieved or not achieved). Both models included fixed effects of genotype (categorical), the first 3 genetic eigenvectors obtained from the genetic principal component analysis (PCA), and selected covariates. The study level type-I error was controlled at 0.05 using the Bonferroni and Hochberg step-up multiplicity adjustment approaches. The Bonferroni adjustment was applied among the six objectives, that is, each objective was tested at 0.05/6 ~= 0.008333 level (two-sided). The rs4149056 C allele was statistically significantly associated with increases in GZR exposure (p-value = 0.00006). The geometric mean ratio (GMR) (95% confidence interval [CI]) of GZR AUC0-24 was 1.13 (1.06, 1.21) for subjects with one copy of the rs4149056 C allele relative to non-carriers, and 1.43 (1.16, 1.77) for subjects with two copies of the rs4149056 C allele relative to non-carriers, respectively. The estimated increases in GZR AUC (and the corresponding upper 95% confidence limits for GMR) associated with the rs4149056 allele were well below the upper clinical comparability bound for GZR AUC. The rs2306283 SNP was not associated with changes in GZR exposure. There was a trend suggesting that the rs11045819 A allele might be associated with decreases in GZR exposure (p-value = 0.03), with an AUC0-24 GMR for the comparisons between subjects with one and two copies of the rs11045819 A allele relative to non-carriers as low as 0.78. However, the estimated effect was not statistically significant after multiplicity adjustment. The estimated decreases in GZR AUC (and the corresponding lower 95% confidence limits for GMR) for rs11045819 A allele carriers compared to non-carriers were well above the lower clinical comparability bound for GZR AUC. There was no evidence suggesting that any of the three examined SNPs (rs4149056, rs2306283 and rs11045819) are associated with SVR12. In conclusion, none of the genetic variants studied have a clinically meaningful effect on pharmacokinetics of GZR or efficacy of EBR/GZR.