Despite well established empiric dose adjustments for drug and disease-state interactions, the impact of body mass index (BM) on warfarin remains unclear. The objective of this study is to evaluate warfarin requirements in hospitalized patients, stratified by BMI. This retrospective review included two cohorts of patients: cohort A (patients admitted with a therapeutic international normalized ratio (INR)) and cohort B (newly initiated on warfarin during hospitalization). Exclusion criteria included: age under 18 years, pregnancy, INR (goal 2.5-3.5), and warfarin thromboprophylaxis post orthopedic surgery. The primary outcome was mean total weekly dose (TWD) of warfarin based on weight classification: underweight (BMI <18 kg/m2), normal/overweight (BMI 18-29.9 kg/m2), obese (BMI 30-39.9 kg/m2), and morbidly obese (BMI ⩾ 40 kg/m2). Data were extracted from two community hospitals in reverse chronologic order during July 2015-June 2013 until both study institutions evaluated 100 patients per cohort in each BMI classification or until all patients had been evaluated within the prespecified timeframe. A total of 585 patients were included in cohort A (26 underweight, 200 normal/overweight, 200 obese, 159 morbidly obese). There was a statistically significant difference in TWD as determined by one-way analysis of variance ( p < 0.05). A Tukey post hoc test revealed a statistically significantly higher TWD in morbidly obese (41.5 mg) compared with underweight (25.6 mg, p < 0.05), normal/overweight (28.8 mg, p < 0.05) and obese patients (32.4 mg, p < 0.05). In cohort B, 379 patients were evaluated (9 underweight, 166 normal/overweight, 152 obese, 52 morbidly obese). Overall, 191 patients had a therapeutic INR on discharge (88.9% underweight, 52.4% normal/overweight, 44.1% obese, 55.8% morbidly obese, p = 0.035). Of those, there was a statistically significant difference in TWD ( p = 0.021) with a higher TWD in the morbidly obese (41 mg) compared with underweight patients (24.4 mg, p = 0.017). Based on the results of this study, morbidly obese patients may require higher TWD to obtain and maintain a therapeutic INR.