Background: Little is known regarding the safety of direct-acting antivirals (DAA), even though they are widely used. This study aims to evaluate the adverse events of DAA using post-market data. Methods: FDA Adverse Events Reporting System (FAERS) data from January 2019 through December 2019 were analyzed. FERAS reports in which the suspected drug contained the DAA drugs were extracted and included in the analysis. Univariable and bivariable analyses were performed in this study. Results: Most of the reported side effects were non-serious (62%). The number of times the drug was reported as ineffective was significantly higher while using Harvoni vs. Mavyret (32.14% vs. 1.05%) (p-value < 0.0001). On the other hand, hospitalization was significantly more reported while using Mavyret compared to Harvoni (52.02% vs. 22.45%) (p-value < 0.0001). Liver cancer was significantly more reported while using Harvoni vs. Mavyret (7.65% vs. 1.20%) (p-value < 0.0001). No significant difference in death cases was reported while using both drugs. Conclusion: Depending on the FDA Adverse Events Reporting System (FAERS) database, most of the non-serious adverse effects were headache and fatigue. There was no significant difference in cases of death reported while using both drugs. Liver cancer was more reported while using Harvoni. Hospitalization was more reported while using Mavyret.