ABSTRACTBackground: Visceral adiposity has been linked to higher rates of cardiometabolic risk than other types of adiposity. Waist circumference (WC) is the best anthropomorphic surrogate of visceral adiposity. Reductions in central adiposity may decrease cardiovascular risk. Animal studies have demonstrated that L-arginine reduces visceral adiposity and fat mass. The primary aim of our study was to assess the efficacy of L-arginine for reducing central adiposity in nondiabetic obese subjects. Secondary aims were to assess the efficacy of L-arginine for decreasing body mass index (BMI), waist-to-hip ratio (WHR), and weight. Materials and Methods: Female subjects (n = 20) were included if they: were ≥ 18 years and ≤ 40 years of age, had a BMI of ≥ 30 and ≤ 40 kg/m2, had a WC ≥ 89 cm. Subjects received 3 g of L-arginine three times a day for 12 weeks and were counseled on lifestyle modification. Results: Overall, L-arginine was well tolerated with no clinically significant adverse events. Serum L-arginine levels were significantly increased from baseline at both 6 and 12 weeks (p < .05). WC (mean ± SD) decreased from 115.6 ± 12.7 cm at baseline to 109.2 ± 11.7 cm at 12 weeks (p = .0004). Weight (mean ± SD) decreased from 98.6 ± 19.7 kg at baseline to 95.7 ± 18.6 kg at 12 weeks (p = .015). Significant reductions from baseline were also observed in BMI and WHR. Conclusions: L-Arginine may be effective at reducing central adiposity in obese patients.