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Objectives: Inappropriate and overuse of antimicrobials, incorrect dosing, and extended duration are some of the leading causes of antibiotic-resistance that have led to the development of antimicrobial resistance (AMR). We aimed to evaluate knowledge, attitudes, and practices regarding rational antibiotic prescribing among physicians in a teaching hospital in Oman, with the goal of identifying knowledge gaps and interventions that could lead to judicious use of antimicrobials and reduce the emergence of resistant organisms METHODS: A cross-sectional study assessing physicians' knowledge of and attitudes towards prescribing antibiotics was conducted at the Royal Hospital from 15 January to 31 March 2020. Likert scales were used to evaluate physicians' awareness and perception of personal performance regarding the care of patients with infections and rational use of antibiotics., Results: Inadequate hand washing was regarded as the most important factor contributing to AMR (51.6%), followed by widespread use of antibiotics (49%), prescribing broad-spectrum antibiotics (47.3%), lack of effective narrow-spectrum antibiotics (47.3%), inappropriate duration of antibiotic therapy (46.2%), inappropriate empirical choice of antibiotics (45.1%), poor access to information on local antibiotic resistance patterns (40.8%), and inadequate restrictions on antibiotic prescribing (34.4%). Other factors contributing to AMR such as lack of local hospital guidelines on antibiotic usage, random mutations in microbes, patient demands and expectations for antibiotics, and the role of pharmaceutical companies in advertising and promoting use of antibiotics were deemed important by 33.3%, 26.8%, 22.5% and 20.4%, respectively., Conclusions: AMR is a global health threat with significant effect on the health system and the economy. Misuse and overuse of antimicrobials remain the main drivers for the development of drug-resistant pathogens. Identifying knowledge gaps and planning interventions that could lead to judicious use of antimicrobials including establishing an Antimicrobial Stewardship Program are of paramount importance in reducing AMR in the twenty-first century and beyond., Competing Interests: Declaration of competing interest All authors declare no conflict of interests related to the current manuscript., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)