Objective The purpose of this cross-sectional study conducted in different private and public sector hospitals of the major cities of Nepal and Pakistan was to compare and evaluate the antibiotic prescribing patterns. Methodology  The data was collected based on prescriptions received from different hospitals of Lahore, Pakistan and Kathmandu, Nepal without much interaction with the patients. Results Out of a total of 272 patients, 111 (40.8%) patients from Nepal and 161 (59.19%) patients from Pakistan were prescribed with 447 antibiotics. In both countries, out of total antibiotics prescribed, 42.30% were 3rd generation cephalosporins. Also, in Pakistan and Nepal, out of all the indications, 49.2% of the antibiotics were given in medical prophylaxis. Conclusion  In Pakistan, the antimicrobial prescription rate is comparatively higher than Nepal, and in both countries, there is a need of proper implementation of antibiotic prescribing guidelines for the prescription of antibiotics and the administration of antibiotics in medical prophylaxis.