BACKGROUND: Frequent emergency department (ED) users account for a disproportionately high number of ED visits. Studies on case management (CM) interventions to reduce frequent ED use have shown mixed results, and few studies have been conducted within a universal health coverage system. To determine whether a CM intervention-compared to standard emergency care-reduces ED attendance. Randomized controlled trial. Two hundred fifty frequent ED users (5 or more visits in the prior 12 months) who visited a public urban ED at the Lausanne University Hospital between May 2012 and July 2013 were allocated to either an intervention (n = 125) or control (n = 125) group, and monitored for 12 months. An individualized CM intervention consisting of concrete assistance in obtaining income entitlements, referral to primary or specialty medical care, access to mental health care or substance abuse treatment, and counseling on at-risk behaviors and health care utilization (in addition to standard care) at baseline and 1, 3, and 5 months. We used a generalized linear model for count data (negative binomial distribution) to compare the number of ED visits during the 12-month follow-up between CM and usual care, from an intention-to-treat perspective. At 12 months, there were 2.71 (+/- 0.23) ED visits in the intervention group versus 3.35 (+/- 0.32) visits among controls (ratio = 0.81, 95 % CI = 0.63; 1.02). In the multivariate model, the effect of the CM intervention on the number of ED visits approached statistical significance (b = -0.219, p = 0.075). The presence of poor social determinants of health was a significant predictor of ED use in the multivariate model (b = 0.280, p = 0.048). CM may reduce ED use by frequent users through an improved orientation to the health care system. Poor social determinants of health significantly increase use of the ED by frequent users.