Objective-Individuals with serious mental illnesses are disproportionately affected by overweight and obesity. Understanding the factors that facilitate or hinder lifestyle change in this population could lead to better interventions and improved health outcomes.Methods-A subset of intervention and usual-care participants (n = 84) in the STRIDE randomized trial were interviewed at 3, 9, and 18 months, yielding 101 interviews (some were interviewed more than once). Participants had a mean age of 48.1 (SD = 10.1); 64% were female. Participants had diagnoses of schizophrenia or schizoaffective disorder (41%), bipolar disorder (20%), affective psychoses (37%) or PTSD (2%). Interviews were transcribed verbatim, coded using Atlas.ti, and analyzed for common themes.Results-Barriers to behavior change were similar to those described for the general population, including lack of support from significant others, the lure of unhealthy foods, and poor weather impeding exercise. Additional challenges included the effects of psychiatric symptoms, or consequences of symptoms (i.e., social isolation), on ability to make and sustain lifestyle changes. We found a strong preference for ongoing, group-based support to foster a sense of accountability which motivated and helped to sustain behavior changes.Conclusions and implications for practice-Individuals with serious mental illnesses encounter many of the same barriers to weight loss seen in the general population, but they may be more vulnerable to additional obstacles. Lifestyle change interventions for this population should help participants develop the ability to iteratively cope with fluctuating mood and subsequent changes in motivation to eat healthfully and exercise regularly.