Background Despite robust weight loss and cardiometabolic benefit, lean mass loss following sleeve gastrectomy (SG) confers health risk. Bisphosphonates are a potential therapeutic agent for lean mass maintenance. Thus, our objective was to explore the effect of 6 months of risedronate (vs. placebo) on change in dual-energy x-ray absorptiometry (DXA)-and computed tomography (CT)-derived lean mass metrics in the year following SG. Methods Twenty-four SG patients were randomized to 6 months of 150-mg oral risedronate or placebo capsules (NCT03411902). Body composition was assessed at baseline and 6 months with optional 12-month follow-up using whole-body DXA and CT at the lumbar spine and mid-thigh. Group treatment effects and 95% confidence intervals (CIs) were generated from a mixed model using contrast statements at 6 and 12 months, adjusted for baseline values.Results Of 24 participants enrolled [55.7 ± 6.7 years (mean ± SD), 79% Caucasian, 83% women, body mass index (BMI) 44.7 ± 6.3 kg/m 2 ], 21 returned for 6-month testing and 14 returned for 12-month testing. Six-month weight loss was À16.3 kg (À20.0, À12.5) and À20.9 kg (À23.7, À18.1) in the risedronate and placebo groups, respectively (P = 0.057). Primary analysis at 6 months revealed a non-significant sparing of appendicular lean mass in the risedronate group compared with placebo [À1.2 kg (À2.3, À0.1) vs. À2.1 kg (À3.0, À1.2)]; P = 0.20. By 12 months, the risedronate group displayed no change in appendicular lean mass from baseline [À0.5 kg (À1.5, 0.6)]; however, the placebo group experienced significantly augmented loss [À2.9 kg (À3.6, À2.1)]. Conclusions Pilot data indicate that risedronate treatment may mitigate appendicular lean mass loss following SG. Further study is warranted.