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Background Marked interindividual variation exists in blood pressure response to benazepril, which is considered to have genetic basis. Our objectives were to evaluate whether the E112D polymorphism in the prolylcarboxypeptidase (PRCP) gene has impact on blood pressure response to benazeprit.Methods Hypertensive patients from Huoqiu County and Yuexi County of Anhui Province received daily treatment with an oral dosage of 10 mg benazepril for 15 days. Genotypes of the E112D polymorphism in the PRCP gene were determined by TaqMan SNP genotyping assay. Multivariate linear and Logistic regressions using generalized estimating equation model were performed in a total of 1092 patients to evaluate the association of PRCP genotypes and blood pressure response to benazepril.Results Patients carrying ED or DD genotype had a less systolic blood pressure reduction (adjusted β= -3.7±1.1, P<0.001), a less diastolic blood pressure reduction (adjusted β= -3.1±0.8, P <0.001) and a lower percentage of reaching target blood pressure defined as SBP lower than 140 mmHg and DBP lower than 90 mmHg (adjusted OR=0.6, P=0.005) than those patients carrying EE genotype. In addition, the results from stratified analysis by county (Huoqiu or Yuexi)were similar to those observed in the pooled population.Conclusions Our data suggest that the El12D polymorphism in the PRCP gene may be a useful genetic marker to predict the antihypertensive effect of short-term benazepril treatment in hypertensive patients of Anhui Province, China.