BackgroundRigorous evaluations of health sector interventions addressing intimate partner violence (IPV) in low- and middle-income countries are lacking. We aimed to assess whether an enhanced nurse-delivered intervention would reduce IPV and improve levels of safety planning behaviors, use of community resources, reproductive coercion, and mental quality of life.MethodsWe randomized 42 public health clinics in Mexico City to treatment or control arms. In treatment clinics, women received the nurse-delivered session (IPV screening, supportive referrals, health/safety risk assessments) at baseline (T1), and a booster counselling session after 3 months (T2). In control clinics, women received screening and a referral card from nurses. Surveys were conducted at T1, T2, and T3 (15 months from baseline). Our main outcome was past-year physical and sexual IPV. Intent-to-treat analyses were conducted via three-level random intercepts models to evaluate the interaction term for treatment status by time.ResultsBetween April and October 2013, 950 women (480 in control clinics, 470 in treatment clinics) with recent IPV experiences enrolled in the study. While reductions in IPV were observed for both women enrolled in treatment (OR, 0.40; 95% CI, 0.28–0.55; P < 0.01) and control (OR, 0.51; 95% CI, 0.36–0.72; P < 0.01) clinics at T3 (July to December 2014), no significant treatment effects were observed (OR, 0.78; 95% CI, 0.49–1.24; P = 0.30). At T2 (July to December 2013), women in treatment clinics reported significant improvements, compared to women in control clinics, in mental quality of life (β, 1.45; 95% CI, 0.14–2.75; P = 0.03) and safety planning behaviors (β, 0.41; 95% CI, 0.02–0.79; P = 0.04).ConclusionWhile reductions in IPV levels were seen among women in both treatment and control clinics, the enhanced nurse intervention was no more effective in reducing IPV. The enhanced nursing intervention may offer short-term improvements in addressing safety planning and mental quality of life. Nurses can play a supportive role in assisting women with IPV experiences.Trial RegistrationClinicaltrials.gov (NCT01661504). Registration Date: August 2, 2012Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0880-y) contains supplementary material, which is available to authorized users.