Abstract Background There are only limited data on sofosbuvir-based treatment regimens in hepatitis C virus (HCV) genotype 4-infected patients. Aims To evaluate safety and efficacy of sofosbuvir-based triple-therapy in HCV genotype 4 infection. Methods All HCV genotype 4-infected patients who started sofosbuvir-based triple-therapy at our two centres between January and June 2014 were prospectively included ( N = 24) and compared to genotype 4 patients treated with peginterferon/ribavirin between January 2001 and December 2012 ( N = 63). Results The demographics in the sofosbuvir group and the controls were comparable (males 87.5% and 82.5%; mean age 46.7 ± 9.0 years and 42.0 ± 9.8 years, respectively). Sustained virological response was achieved in 83.3% in the sofosbuvir group and in 47.6% of controls ( P = 0.003). Fatigue ( P = 0.007), flu-like ( P = 0.015), gastrointestinal ( P < 0.001), dermatologic ( P < 0.001) and psychiatric symptoms ( P = 0.022) were more common in the control group. Conclusions In our real-life cohort, sofosbuvir-based triple therapy confirmed its high efficacy and safety for chronic genotype 4 hepatitis C.