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Objective: The study aimed to assess the safety profile of Direct Acting Anti-Viral’s (DAAs) among patients with chronic Hepatitis C Virus (HCV). Methods: This multicenter, analytical cross-sectional study was conducted in six gastroenterology and Hepatology centers including Liver Center Faisalabad, Allama Iqbal Medical Institute and Liver Center DHQ Hospital Sialkot, Isra Hospital Hyderabad, Allied Hospital Faisalabad and Rehman Medical Institute Peshawar, between May 2018 and May 2019. The data regarding patient demographics, treatment plan and the frequency of Adverse Events (AEs), and their severity was collected using a pre-designed questionnaire and analyzed through SPSS version 20.0. Results: A total of 511 HCV patients were enrolled, with an overall male majority. Around 66.3% patients experienced a total of 419 AEs, out of which 61 events were suspected from DAAs while remaining 317 events were associated with Ribavirin. Pyrexia (24.6%) and fatigue (14.8%) were the most commonly reported AEs among patients receiving DAAs. Factors such as Ribavirin-based treatments and the presence of Cirrhosis were more likely to promote AEs occurrence OR [95%CI] i.e. 5.2(2.3-9.1) and 1.9(1.1-3.1) respectively (p < 0.05). Conclusion: It is concluded from the study results that DAAs have displayed promising outcomes due to the minimal and minor AEs reported. doi: https://doi.org/10.12669/pjms.37.2.3400 How to cite this:Hashmi ZY, Zia MQ, Bajwa A, Ahmed M, Anwer N, Raza M, et al. New drugs and new concerns: Gaining insight through Pharmacovigilance of direct acting Anti-Viral’s in chronic HCV patients. Pak J Med Sci. 2021;37(2):299-304. doi: https://doi.org/10.12669/pjms.37.2.3400 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.