Background:Frequent antibiotic prescription in high-risk departments, such as orthopedics, significantly contributes to the global surge in antibiotic resistance. Nevertheless, scant studies delineate antibiotic prescribing patterns and trends among orthopedic inpatients. Aim:This study aims to meticulously compare and elucidate the patterns and trends of antibiotic prescriptions over a decade for orthopedic inpatients in a teaching care hospital in Western India. Methods: Data from more than 6000 orthopedic inpatients were meticulously collected using a prospective cross-sectional study design. Patterns were meticulously compared based on indications, corresponding antibiotic treatments, mean Defined Daily Doses (DDD)/1000 patient-days, adherence to the National List of Essential Medicines India (NLEMI), and the World Health Organization Model List of Essential Medicines (WHOMLEM). Antibiotic prescriptions were meticulously analyzed separately for operated and non-operated inpatients. Linear regression was meticulously employed to analyze the time trends of antibiotic prescribing; overall through DDD/1000 patient-days and by antibiotic groups. Results: In the teaching hospital, 65% of inpatients were male, with 53% receiving antibiotic prescriptions. Adherence to the WHO Model List of Essential Medicines (WHOMLEM) was 65%, surpassing the National List of Essential Medicines of India (NLEMI) at 31%. Fixed-dose combinations (FDCs) constituted 35% of prescriptions. Third-generation cephalosporins emerged as the most prescribed antibiotic class (TH-39%), with fractures being the most common indication (TH-48%). A significant majority of operated inpatients (TH-99%) received pre-operative prophylactic antibiotics. Non-operated inpatients also received antibiotics (TH-40%), despite a limited number having infectious diagnoses (TH-8%). Adherence to NLEMI was lower (TH-31%) than WHOMLEM (TH-65%) in both hospitals. Mean DDD/1000 patient-days was 16 times higher in TH (2658) compared to NTH (162). Conclusion: A substantial number of inpatients received antibiotics without clear infectious indications. Adherence to NLEMI and WHOMLEM was low in both hospitals. Antibiotic use increased over 10 years in both hospitals, with higher rates in TH. This underscores the imperative need for developing and implementing local antibiotic prescribing guidelines.