Background: World Health Organization defines Adverse Drug Reaction as “any noxious, unintended, and undesired effect of a drug, which occurs to normal doses used in humans for prophylaxis, diagnosis, or therapy”. ADRs are the most common cause of morbidity, mortality, and poor therapeutic outcomes. Therefore, pharmacovigilance is very important to monitor the risk and benefits of pharmaceutical products after they have been launched into the market. Objective: The objective of this study was to evaluate the knowledge, attitude, and practices of medical practitioners on pharmacovigilance and ADR reporting system in Malaysia and also to elucidate the factors leading to underreporting of ADRs. Methods: A cross-sectional survey study was conducted among 600 private and public medical practitioners of Kuala Lumpur and Selangor, using a structured and validated questionnaire to collect the respondent’s demographic details and KAP on ADR reporting. A convenience sampling technique was used to recruit the sample size. Results: In this study, a total of 600, that is 300 practitioners each from the private and public medical facilities completed the questionnaire. The knowledge assessment showed that 94.83% (Private medical practitioners- n=281, 93.67%; public medical practitioners- n=288, 96%) of respondents believe ADR reporting helps to identify safe drugs and 91.33% (Private medical practitioners- n=276, 92%; public medical practitioners- n=272, 90.67%) said it helps to measure ADR incidence. Regarding practice, 94% (Private medical practitioners- n=287, 95.67%; public medical practitioners- n=277, 92.33%) of respondents were willing to report an incident only if they were confident that the reaction is an ADR. Around 251 (83.67%) private and 266 (88.67%) public medical practitioners suspected an ADR, but they did not report it. Conclusion: The study concluded that around half of the participants were having an average to moderate level of knowledge, attitude, belief, and practice toward ADR reporting. Underreporting of ADR was observed at all levels of practice; hence, an extensive intervention is needed to rule out the root cause of underreporting and to improve the rate of ADR reporting. Keywords: Pharmacovigilance, adverse reactions, side effects, spontaneous reporting, practitioners.