Objective: Weight reduction programs are not generally designed or adapted for people with physical disabilities. This study examined the effect of a 9-months remote, telephone-based weight management program for people with physical disabilities using a Web-based system (Personalized Online Weight and Exercise Response System [POWERS]). Design: A total of 102 participants (mean ± SD age, 46.5 ± 12.7 yrs; body mass index, 32.0 ± 5.8 kg/m) with a physical disability (spinal cord injury, multiple sclerosis, spina bifida, cerebral palsy, stroke, or lupus) were randomized to one of three conditions: physical activity only (POWERS), physical activity plus nutrition (POWERSplus), and control. The POWERS group received a physical activity tool kit and regular coaching telephone calls. The POWERS plus group received an intervention identical to that of the POWERS group plus nutritional information. The control group received the physical activity tool kit and self-guided health promotion resources at the completion of the trial but no coaching. Results: Postintervention differences in body weight were found between the groups. There was a significant group × time interaction (P < 0.01) in postintervention body weight, with both the POWERS and POWERSplus groups demonstrating greater reduction in body weight compared with the control group (POWERS: -2.1 ± 5.5 kg, -2.4 ± -5.9%; POWERSplus: -0.5 ± 5.0 kg, -0.6 ± 4.3%; control: +2.6 ± 5.3 kg, 3.1 ± 7.4%). Conclusions: A low-cost telephone intervention supported with a Web-based remote coaching tool (POWERS) can be an effective strategy for assisting overweight adults with physical disabilities in maintaining or reducing their body weight. Copyright © 2013 Lippincott Williams & Wilkins.