Intensive early treatment for first-episode psychosis has been shown to be effective. It is unknown if the positive effects are sustained for 5 years. To determine the long-term effects of an intensive early-intervention program (OPUS) for first-episode psychotic patients. Single-blinded, randomized, controlled clinical trial of 2 years of an intensive early-intervention program vs standard treatment. Follow-up periods were 2 and 5 years. Copenhagen Hospital Corporation and Psychiatric Hospital, Aarhus, Denmark. Patients A total of 547 patients with a first episode of psychosis. Of these, 369 patients were participating in a 2-year follow-up, and 301 were participating in a 5-year follow-up. A total of 547 patients were followed for 5 years. Two years of an intensive early-intervention program vs standard treatment. The intensive early-intervention treatment consisted of assertive community treatment, family involvement, and social skills training. Standard treatment offered contact with a community mental health center. Psychotic and negative symptoms were recorded. Secondary outcome measures were use of services and social functioning. Analysis was based on the principles of intention-to-treat. Assessment was blinded for previous treatment allocation. At the 5-year follow-up, the effect of treatment seen after 2 years (psychotic dimension odds ratio [OR], -0.32; 95% confidence interval [CI], -0.58 to -0.06; P = .02; negative dimension OR, -0.45; 95% CI, -0.67 to -0.22; P = .001) had equalized between the treatment groups. A significantly smaller percentage of patients from the experimental group were living in supported housing (4% vs 10%, respectively; OR, 2.3; 95% CI, 1.1-4.8; P = .02) and were hospitalized fewer days (mean, 149 vs 193 days; mean difference, 44 days; 95% CI, 0.15-88.12; P = .05) during the 5-year period. The intensive early-intervention program improved clinical outcome after 2 years, but the effects were not sustainable up to 5 years later. Secondary outcome measures showed differences in the proportion of patients living in supported housing and days in hospital at the 5-year follow-up in favor of the intensive early-intervention program.