Importance: Long-term exercise benefits on prevalent adverse events in older populations, such as falls, fractures, or hospitalizations, are not yet established or known.Objective: To systematically review and investigate the association of long-term exercise interventions (≥1 year) with the risk of falls, injurious falls, multiple falls, fractures, hospitalization, and mortality in older adults.Data sources: PubMed, Cochrane Central Register of Controlled Trials, SportDiscus, PsychInfo, and Ageline were searched through March 2018.Study selection: Exercise randomized clinical trials (RCTs) with intervention length of 1 year or longer, performed among participants 60 years or older.Data extraction and synthesis: Two raters independently screened articles, abstracted the data, and assessed the risk of bias. Data were combined with risk ratios (RRs) using DerSimonian and Laird's random-effects model (Mantel-Haenszel method).Main outcomes and measures: Six binary outcomes for the risk of falls, injurious falls, multiple falls (≥2 falls), fractures, hospitalization, and mortality.Results: Forty-six studies (22 709 participants) were included in the review and 40 (21 868 participants) in the meta-analyses (mean [SD] age, 73.1 [7.1] years; 15 054 [66.3%] of participants were women). The most used exercise was a multicomponent training (eg, aerobic plus strength plus balance); mean frequency was 3 times per week, about 50 minutes per session, at a moderate intensity. Comparator groups were often active controls. Exercise significantly decreased the risk of falls (n = 20 RCTs; 4420 participants; RR, 0.88; 95% CI, 0.79-0.98) and injurious falls (9 RTCs; 4481 participants; RR, 0.74; 95% CI, 0.62-0.88), and tended to reduce the risk of fractures (19 RTCs; 8410 participants; RR, 0.84; 95% CI, 0.71-1.00; P = .05). Exercise did not significantly diminish the risk of multiple falls (13 RTCs; 3060 participants), hospitalization (12 RTCs; 5639 participants), and mortality (29 RTCs; 11 441 participants). Sensitivity analyses provided similar findings, except the fixed-effect meta-analysis for the risk of fracture, which showed a significant effect favoring exercisers (RR, 0.84; 95% CI, 0.70-1.00; P = .047). Meta-regressions on mortality and falls suggest that 2 to 3 times per week would be the optimal exercise frequency.Conclusions and relevance: Long-term exercise is associated with a reduction in falls, injurious falls, and probably fractures in older adults, including people with cardiometabolic and neurological diseases.