IMPORTANCE: Bipolar disorder-specific psychotherapy combined with pharmacotherapy improves relapse risk, symptom burden, and quality of life, but psychotherapy is not easily accessible. OBJECTIVE: To determine if a smartphone-based self-management intervention (LiveWell) can assist individuals with bipolar disorder to maintain wellness. DESIGN, SETTING, AND PARTICIPANTS: An assessor-blind randomized clinical trial enrolled participants from March 20, 2017, to April 25, 2019, with 48-week follow-up ending on April 10, 2020. Participants were randomly assigned to usual care or usual care plus the smartphone intervention stratified by relapse risk based on initial clinical status (low risk: asymptomatic recovery; high risk: continued symptomatic, prodromal, recovering, symptomatic recovery). Participants with bipolar disorder I were recruited from clinics in the Chicago and Minneapolis-Saint Paul areas. Data were analyzed from June 19, 2020, to May 25, 2022. INTERVENTIONS: The smartphone-based self-management intervention consisted of an application (app), coach, and website. Over 16 weeks, participants had a coach visit followed by 6 phone calls, and they completed daily and weekly app check-ins. The app provided adaptive feedback and information for developing a personalized wellness plan, the coach provided support, and the website provided summary data and alerts. MAIN OUTCOMES AND MEASURES: The primary outcome was time to relapse. Secondary outcomes were percentage-time symptomatic, symptom severity, and quality of life. RESULTS: Of the 205 randomized participants (mean [SD] age, 42 [12] years; 125 female individuals [61%]; 5 Asian [2%], 21 Black [10%], 13 Hispanic or Latino [6%], 7 multiracial [3%], 170 White [83%], 2 unknown race [1%]), 81 (40%) were randomly assigned to usual care, and 124 (60%) were randomly assigned to usual care plus the smartphone intervention. This clinical trial did not detect a reduction in relapse risk for the smartphone intervention (hazard ratio [HR], 0.65; 95% CI, 0.39-1.09; log-rank P = .08). However, decreased relapse was observed for low-risk individuals (HR, 0.32; 95% CI, 0.12-0.88; log-rank P = .02) but not high-risk individuals (HR, 0.86; 95% CI, 0.47-1.57; log-rank P = .62). Reduced manic symptom severity was observed for low-risk individuals (mean [SE] difference, -1.4 [0.4]; P = .001) but not for high-risk individuals (mean [SE] difference, 0 [0.3]; P = .95). The smartphone-based self-management intervention decreased depressive symptom severity (mean [SE] difference, -0.80 [0.34]; P = .02) and improved relational quality of life (mean [SE] difference, 1.03 [0.45]; P = .02) but did not decrease percentage-time symptomatic (mean [SE] difference, -5.6 [4.3]; P = .20). CONCLUSIONS AND RELEVANCE: This randomized clinical trial of a smartphone-based self-management intervention did not detect a significant improvement in the primary outcome of time to relapse. However, a significant decrease in relapse risk was observed for individuals in asymptomatic recovery. In addition, the intervention decreased depressive symptom severity and improved relational quality of life. These findings warrant further work to optimize the smartphone intervention and confirm that the intervention decreases relapse risk for individuals in asymptomatic recovery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03088462.