ImportanceThere is little information on upstream community-based interventions that reduce the prevalence of handgun carrying among adolescents, especially those growing up in rural areas.ObjectiveTo test whether Communities That Care (CTC), a community-based prevention system focusing on risk and protective factors for behavioral problems early in life, reduces handgun carrying prevalence among adolescents growing up in rural areas.Design, Setting, and ParticipantsCommunity-randomized trial of 24 small towns in 7 states assigned randomly to the CTC or control group with outcomes assessed from 2003 to 2011. Participants were youths attending public schools in grade 5 who received consent from their parents to participate (77% of the eligible population) and were repeatedly surveyed through grade 12 with 92% retention. Analyses were conducted from June to November 2022.InterventionsA coalition of community stakeholders received training and technical assistance to install CTC, used local epidemiologic data to identify elevated risk factors and low protective factors for adolescent behavioral problems, and implemented tested preventive interventions for youth, their families, and schools.Main Outcomes and MeasuresHandgun carrying (never vs at least once) operationalized in 2 ways: (1) prevalence of past-year handgun carrying, and (2) cumulative prevalence of handgun carrying from grade 6 through grade 12.ResultsOverall, the 4407 study participants’ mean (SD) age was 12 (.4) years in both CTC (2405 participants) and control (2002 participants) communities in grade 6; about one-half of participants in each group were female (1220 [50.7 %] in the CTC group and 962 [48.1%] in the control group). From grade 6 through grade 12, 15.5% of participants in CTC communities and 20.7% of those in control communities reported carrying a handgun at least once. Youths in CTC communities were significantly less likely to report handgun carrying at a given grade than those in control communities (odds ratio [OR], 0.73; 95% CI, 0.65-0.82). The most pronounced effects were observed in grade 7 (OR, 0.70; 95% CI, 0.42-0.99), grade 8 (OR, 0.58; 95% CI, 0.41-0.74), and grade 9 (OR, 0.65; 95% CI, 0.39-0.91). Cumulatively from grade 6 through grade 12, youths in CTC communities were significantly less likely to report handgun carrying at least once than those in control communities (OR, 0.76; 95% CI, 0.70-0.84). Overall, CTC reduced the prevalence of past-year handgun carrying by 27% at a given grade and by 24% cumulatively through grade 12.Conclusions and RelevanceIn this study, CTC reduced the prevalence of adolescent handgun carrying in participating communities.Trial RegistrationClinicalTrials.gov Identifier: NCT01088542