Adverse drug reactions (ADRs) significantly affect patient safety and healthcare spending worldwide. Hospital pharmacists are uniquely positioned to address ADRs due to their crucial role in medication management. However, underreporting remains a global concern, especially in developing countries, where pharmacovigilance systems are inadequately developed. Therefore, this pilot study aimed to evaluate and compare the knowledge, attitudes, perceived barriers, and facilitators regarding ADR reporting by hospital pharmacists in a developed (US) and a developing (Pakistan) country. A cross-sectional survey was conducted, using a pre-validated questionnaire. The pharmacists, possessing a minimum of one year's hospital experience, were selected via convenience sampling. Out of 151 respondents, included in the final analysis (US: = 51; Pakistan: = 100), the majority were female (62.3%), aged 29-35 years (38%), and possessed a Pharm. D degree (49.7%). The knowledge (US: 6.03 ± 0.27 vs. Pakistan:5.69 ± 0.25, -value = 0.193) and attitude scores (US: 32.02 ± 0.73 vs. Pakistan: 32.63 ± 0.67; -value = 0.379) exhibited no significant differences between the groups. Nonetheless, barriers at both the individual and systemic levels were more pronounced in the developing country. Important facilitators reported were mobile applications for ADR reporting, specialized training, and intuitive reporting tools. In conclusion, we found that pharmacists in both settings exhibit comparable knowledge and positive attitudes towards ADR reporting, though specific contextual barriers are present. Interventions customized to the local hospital infrastructure are crucial for enhancing ADR reporting, particularly in resource-constrained settings.