Introduction: This study examines the feasibility and effectiveness of an intensive lifestyle intervention adapted for people with impaired mobility. Study design: This was a randomized, wait-list controlled trial. The experimental group immediately received the 12-month weight loss program; the wait-list control group received it after a 6-month delay. Between-group comparisons were conducted for the 6-month RCT study design. Repeated measures were conducted for both groups combined after receiving the 12-month intervention. Data were collected August 2015–February 2017 and analyzed in 2017. Setting/participants: A community-based sample received 23, group-based sessions via a mix of telephone and in-person sessions in a hospital-based setting. Participants with impaired mobility (n=66) were middle-aged (49.80 [SD=11.37] years), mostly White (66.7%), female (66.7%), and most commonly had spinal cord injury (47.0%). Intervention: The 12-month intervention delivered 23 group-based sessions that promoted weight loss through reducing caloric intake and increasing physical activity. Main outcome measures: Primary outcomes were effectiveness measured as change in weight and time spent in moderate physical activity. Feasibility was assessed in 12-month combined group analyses, measured as retention, attendance, and dietary self-monitoring. Results: The 6-month RCT results showed that the immediate and delayed groups differed significantly (p<0.05) in weight (−1.66 [SD=4.42] kg loss vs 0.05 [SD=4.15] kg gain) and moderate physical activity (52.93 [SD=90.74] minutes/week increase vs −14.22 [SD=96.02] minutes/week decrease), accounting for baseline weight, time with disability, and age of onset. The 12-month results with groups combined demonstrated 74.2% retention and 77.7% core session attendance. Self-monitoring was higher in the delayed group (77.3%), who used a smartphone app, than the immediate group (47.3%), who mostly used paper trackers. Participants achieved significant 12-month weight loss of 3.31 (SD=10.13) kg (d=0.33) in mixed modeling analyses with groups combined yet did not significantly increase moderate physical activity. Conclusions: Group Lifestyle Balance Adapted for Individuals with Impaired Mobility is a feasible, effective approach to teach healthy lifestyle skills to individuals with mobility impairment, yielding modest weight loss and enhanced self-efficacy. Trial registration: This study is registered at www.clinicaltrials.gov NCT03307187.