BACKGROUND Direct acting antivirals (DAAs) are a very effective treatment for hepatitis C virus (HCV). However, brand DAAs are expensive. The licensing of cheaper generic DAAs may address this issue, but there is a lack of clinical studies comparing the efficacy of generic vs brand DAA formulations. AIM To compare the efficacy and safety of generic against brand DAAs for chronic hepatitis C treatment in Bahrain. METHODS This was a retrospective observational study involving 289 patients with chronic HCV infection during 2016 to 2018. There were 149 patients who were treated with brand DAAs, while 140 patients were treated with generic DAAs. Commonly used DAAs were Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir ± Ribavirin, and Sofosbuvir/Daclatasvir ± Ribavirin. SVR at 12 wk post treatment was the main outcome variable. RESULTS Overall, 87 patients (30.1%) had cirrhosis and 68.2% had genotype 1 HCV infection. At 12 wk post treatment, SVR was achieved by 271 (93.8%) of the patients. In patients who were treated with generic medications, 134 (95.7%) achieved SVR at 12 wk post treatment, compared to 137 (91.9%) among those treated with brand medications ( P = 0.19). Having cirrhosis [odds ratio (OR): 9.41, 95% confidence interval (CI): 2.47–35.84] and having HCV genotype 3 (OR: 3.56, 95%CI: 1.03–12.38) were significant independent predictors of not achieving SVR. Alanine transaminase, gamma-glutamyl transpeptidase, and total bilirubin levels decreased significantly following therapy with both generic and brand DAAs. CONCLUSION Generic and brand DAAs demonstrate comparable effectiveness in the treatment of chronic hepatitis C patients. Both are safe and equally effective in improving biochemical markers of hepatic inflammation.