Background Critically ill patients are at risk of developing a postintensive care syndrome (PICS), which is characterized by physical, psychological, and cognitive impairments and which dramatically impacts the patient’s quality of life (QoL). No intervention has been shown to improve QoL. We hypothesized that a medical, psychological, and social follow-up would improve QoL by mitigating the PICS. Objective This multicenter, randomized controlled trial (SUIVI-REA) aims to compare a multidisciplinary follow-up with a standard postintensive care unit (ICU) follow-up. Methods Patients were randomized to the control or intervention arm. In the intervention arm, multidisciplinary follow-up involved medical, psychological, and social evaluation at ICU discharge and at 3, 6, and 12 months thereafter. In the placebo group, patients were seen only at 12 months by the multidisciplinary team. Baseline characteristics at ICU discharge were collected for all patients. The primary outcome was QoL at 1 year, assessed using the Euro Quality of Life-5 dimensions (EQ5D). Secondary outcomes were mortality, cognitive, psychological, and functional status; social and professional reintegration; and the rate of rehospitalization and outpatient consultations at 1 year. Results The study was funded by the Ministry of Health in June 2010. It was approved by the Ethics Committee on July 8, 2011. The first and last patient were randomized on December 20, 2012, and September 1, 2017, respectively. A total of 546 patients were enrolled across 11 ICUs. At present, data management is ongoing, and all parties involved in the trial remain blinded. Conclusions The SUVI-REA multicenter randomized controlled trial aims to assess whether a post-ICU multidisciplinary follow-up improves QoL at 1 year. Trial Registration Clinicaltrials.gov NCT01796509; https://clinicaltrials.gov/ct2/show/NCT01796509 International Registered Report Identifier (IRRID) DERR1-10.2196/30496