Objective To determine the factors that predict change in well-being over time in older men and women presenting to the falls prevention clinic. Design Prospective cohort study. Setting Falls prevention clinic. Participants Community-dwelling older adults who were referred to the clinic after sustaining a fall (between N=244 and N=255, depending on the analysis). Interventions Not applicable. Main Outcome Measures The ICEpop CAPability measure for Older people, a measure of well-being or quality of life, was administered at baseline, 6 months, and 12 months. We constructed linear mixed models to determine whether baseline predictor variables were related to baseline well-being and/or changes in well-being over time. In addition, we included interactions with sex to investigate the difference between men and women. Baseline predictors included 2 measures of mobility—Short Performance Physical Battery and timed Up and Go test—and a measure of global cognitive function—Montreal Cognitive Assessment. Results All 3 predictors were associated with well-being at baseline (P<.05). Furthermore, both the Short Performance Physical Battery and the timed Up and Go test interacted with sex (P<.05) to predict changes in well-being over time. Follow-up analyses suggested that better mobility was protective against decline in well-being in men but was generally unrelated to changes in well-being in women. Conclusions We found that 2 valid and reliable measures of mobility interacted with sex to predict changes in well-being over time. This is a critical research area to develop in order to appropriately tailor future intervention strategies targeting well-being in older fallers, a population at high risk of functional decline.