Background: Increasing protein content of the diet might be an effective strategy to preserve muscle mass in older adults undergoing caloric restriction, thereby preserving muscle function. Methods: Ninety-six older adults (70.3 ± 3.7 years, 74% women, 27% African American) with obesity (35.4 ± 3.3 kg/m 2 ; 47% total body fat) were randomized to a 6-month higher protein (providing 1.2-1.5 g/kg/d) weight loss (WL) program, utilizing the Medifast 4&2&1 Plan, or to weight stability (WS). Dual-energy x-ray absorptiometry-acquired total body mass and composition, and fast gait speed over 400 m was assessed at baseline, 3, and 6 months. Results: At baseline, dual-energy x-ray absorptiometry-acquired total body, fat, and lean masses were 95.9 ± 14.6, 44.6 ± 7.6, and 48.7 ± 9.5 kg, respectively, and 400-m gait speed was 1.17 ± 0.20 m/s. Total body mass was significantly reduced in the WL group (−8.17 [−9.56, −6.77] kg) compared with the WS group (−1.16 [−2.59, 0.27] kg), with 87% of total mass lost as fat (WL: −7.1 [−8.1, −6.1] kg; −15.9% change from baseline). A differential treatment effect was not observed for change in lean mass (WL: −0.81 [−1.40, −0.23] kg vs WS: −0.24 [−0.85, 0.36] kg). Four-hundred-meter gait speed was also unchanged from baseline although trends suggest slightly increased gait speed in the WL group [0.01 (−0.02, 0.04) m/s] compared with the WS group [−0.02 (−0.05, 0.01) m/s]. Conclusion: Intentional weight loss using a high-protein diet is effective in producing significant total body mass and fat mass loss, while helping preserve lean body mass and mobility, in relatively high-functioning older adults with obesity.