OBJECTIVES: Two NS3/4A protease inhibitors (PIs), telaprevir and boceprevir, were recently approved in the United States. Even though several randomized controlled trials (RCTs) have demonstrated the efficacy and safety of PIs, a meta-analysis using various subgroup analyses based on patient characteristics has not been conducted. The objectives were to compare the efficacy and safety of these PIs in patients with chronic hepatitis C genotype 1, based on PI type and patient characteristics. METHODS: Both published and unpublished RCTs were selected if they: 1) compared triple therapies (telaprevir or boceprevir + peg-interferon + ribavirin) and dual therapy (peg-interferon + ribavirin); 2) had treatment groups that met FDA-approved dosages; and 3) measured the outcome using sustained virologic response (SVR). RESULTS: A total of 4421 patients from 10 evaluated articles were included in the meta-analysis. Overall, triple therapy was significantly associated with a higher achievement of SVR than dual therapy (odds ratio [OR] = 3.959; 95% confidence interval [CI], 3.146 to 4.981). When administering triple therapy, the likelihood of achieving SVR in telaprevir-treated patients (OR = 4.292; 95% CI, 2.893 to 6.369) was significantly different than that in boceprevir-treated patients (OR = 3.634; 95% CI, 2.777 to 4.754). The likelihood of achieving SVR with triple therapy compared to dual therapy was statistically significantly higher in treatment-experienced patients (OR = 7.544; 95% CI, 5.919 to 9.615) compared to treatment-naïve patients (OR = 3.026; 95% CI, 2.641 to 3.466). Patients on triple therapies had an increased incidence of treatment discontinuation attributable to adverse events when compared with the dual therapy, regardless of PI type and patients’ treatment experience. CONCLUSIONS: Regarding achieving SVR, triple therapies including either PI are superior to dual therapy for both previously untreated and previously treated patients.