ABSTRACT: BACKGROUND:Intimate partner violence (IPV) is linked to substance use by male perpetrators and is associated with an increased risk of depression for women who experience violence. Unite for a Better Life (UBL) is a gender-transformative intervention delivered to men, women, and couples in Ethiopia; previous evidence demonstrated the intervention significantly reduced experience of and perpetration of IPV when delivered to men and led to more equitable household task-sharing when delivered to men and couples. The aim of this analysis is to assess engagement in the UBL intervention and to examine the relationship between random assignment to the intervention and men's past-year substance use and women's reported depressive symptoms as measured at the individual level. METHODS AND FINDINGS:A sample of 64 villages in Gurague zone, Ethiopia, was randomly allocated to 4 arms (men's UBL, women's UBL, couples' UBL, or control). In each village, 106 households were randomly sampled, and households in the intervention arms were invited to participate in UBL, consisting of 14 sessions delivered by trained facilitators. Households in the control arm were offered a short educational session on IPV. Descriptive data on participant engagement in the intervention are reported, and outcomes assessed in an intention-to-treat (ITT) analysis include male use of substances (alcohol and khat) and women's depressive symptoms as measured by the Patient Health Questionnaire (PHQ-9). Results from both adjusted and unadjusted specifications are reported, the latter adjusting for baseline covariates including age, education level, marriage length, polygamy, socioeconomic status, months between intervention and endline, and the baseline level of the outcome variable. The baseline sample includes 6,770 respondents surveyed in 2014-2015, and follow-up data were available from 88% of baseline respondents surveyed in 2017-2018; the majority of respondents report no education, and 61% are Muslim. Respondents reported high attendance rates and engagement in the intervention. In addition, there was evidence of a significant reduction in frequent past-year alcohol intoxication self-reported by men (adjusted odds ratio [AOR] = 0.56, 95% CI 0.36-0.85, p = 0.007), and a significant increase in the probability of frequent khat use self-reported by men (AOR = 3.09, 95% CI 1.37-6.96, p = 0.007), both observed in the couples' UBL arm at 24 months' follow-up relative to the control arm. There was a significant increase in symptoms of moderate depression among women in the women's UBL arm only (AOR = 1.65, 95% CI 1.13-2.41, p = 0.010), again relative to the control arm. There was no evidence of shifts in symptoms of mild or severe depression. The primary limitation of this study is the reliance on self-reported data around sensitive behaviors. CONCLUSIONS:The findings suggest that the UBL intervention was associated with a reduction in men's use of alcohol when delivered to couples, but there was no evidence of a decrease in reported symptoms of depression among women in any experimental arm, and some evidence of an increase in symptoms of moderate depression in the women's UBL arm. Further research should explore how to optimize IPV prevention interventions to target related risks of mental health and substance use. TRIAL REGISTRATION:Clinicaltrials.gov NCT02311699; Socialscienceregistry.org AEARCTR-0000211.