Objectives: To examine the influences from life stress and the hypothesized protective variables of social competence, family functioning, and peer social engagement on quality of life (QL) in adolescents with mobility disabilities within a stress-resilience model. Methods: Variables were assessed with questionnaires completed by 159 adolescents with a mobility disability (aged 11-18 years) and their parents. Both more subjective and objective QL measures were completed using both adolescent and parent reports. Results: Increased life stress was associated with worse QL. Hypothesized protective variables were used to explain significant variance in more subjective, but not objective, measures of QL beyond covariates and life stress. The hypothesized protective variables, however, did not moderate the effects of life stress on QL. There was a cumulative effect from the hypothesized protective variables such that adolescents with more of these factors had more subjective QL than those with just one factor, regardless of the specific factor. Conclusions: Consistent with the tested model, interventions to improve QL in adolescents with a mobility disability may focus on reducing life stress and developing resilience by enhancing a variety of personal and social resources. © The Author 2006. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved.