Introduction Interferon-based therapies against the hepatitis C virus had a poor adherence profile. On the other hand, new direct-acting antivirals (DAAs) are orally administered medications, show high efficacy against the hepatitis C virus in addition to a high safety profile. Therefore, adherence to this treatment is expected to improve. Assessment for treatment adherence is mandatory to assess the feasibility of achieving viral hepatitis elimination. Aim The study aims to assess the adherence rate and causes of non-adherence in Egyptian hepatitis C patients who received interferon-free treatment regimens. Methods Retrospective data analysis for 668 hepatitis C patient’s records from August 2014 to October 2019 was done. Assessment of treatment adherence was done by revising the records and phone calls. However, 172 patients were excluded due to the absence of contact data. Rest of patients (n = 496) was categorized into 2 groups: Adherent (n = 432) and non-adherent (n = 64). For whom comparative analysis was done. Results The adherent group (87%) achieved 100 % sustained virological response after 12 weeks (SVR 12). Non-adherence was reported in 12.9% of patients. Low awareness was the main cause of non-adherence (43.75%). BMI was the only significant risk factor for poor adherence ( P = . 04). Other Patient demographics, clinical, and laboratory data didn’t show any significant differences between both groups. Conclusion Interferon-free regimens are tolerable. Raising awareness is mandatory for proper treatment adherence and, subsequently, good clinical outcomes.