Ethics committees (ECs) work toward upholding rights, dignity, safety, and well-being of research participants. They are also tasked with conducting oversight pre- and post-approval. ECs face various challenges in their functioning. Post-approval oversight is one of the major challenges, and various studies have stressed the importance of post-approval oversight. The aim of this study was to explore the challenges in the post-approval processes that are faced by the ECs and to suggest solutions to the most common challenges. We conducted a quantitative study contacting member secretaries of different ECs using an online Google Forms questionnaire. The questionnaire consisted of three domains and included questions about the description of the EC, conduct of post-approval activities, and challenges encountered during the post-approval process. We received responses from 61 member secretaries. We were able to identify challenges faced by the EC members in the post-approval process in the areas of site monitoring visit, review of post-approval submission (nonsubmission/incomplete submission/late submission of documents by PI, long time taken by reviewers, nonavailability of reviewers, nonadherence to timeline and too much paperwork), review of serious adverse events, and review of protocol deviations. Our study also noted the difference between accredited/assessed (National Accreditation Board for Hospitals and Healthcare Providers/Forum for Ethical Review Committees in the Asian and Western Pacific Region) ECs versus registered (Central Drugs Standard Control Organisation/Department of Health Research only) ECs by comparing the challenges.