Low doses of ketamine are commonly used to decrease opiates tolerance, hyperalgesia and delirium in perioperative theatre but these properties have never been studied in intensive care unit (ICU) patients. To determine the impact of ketamine infusion on opiates consumption when added to standard care in ICU patients requiring sedation for mechanical ventilation. Patients admitted in a general ICU of a university hospital and undergoing mechanical ventilation ( n = 162) with nurse-driven sedation protocol were randomly assigned into ketamine (2 mg/kg/h) or placebo in a double-blinded control trial. Patients were assessed for sedation and analgesia levels, opiates consumption and delirium (using the Confusion Assessment Method for ICU). Daily consumption of remifentanil (7.9 ± 1.0 vs. 9.3 ± 1.0 μg/kg/h, P = 0.548) and increase in remifentanil doses required for equianalgesia (0.107 ± 0.17 and 0.11 ± 0.18 μg/kg/min, P = 0.78) were not different between ketamine and control groups. The incidence was higher in the placebo group 30/82 (37%) than in the ketamine group 17/80 (21%) ( P = 0.03). The duration of delirium was lower in ketamine group (5.3 ± 4.7 vs. 2.8 ± 3 days, P = 0.005). Mortality rates, ventilator-free days and ICU length of stay (LOS) were non-statistically different in both groups. When the best practices of sedation (nurse-driven sedation, a consistent light-to-moderate sedation level, and delirium monitoring) are used for all patients, the addition of low doses of ketamine does not decrease opiate consumption but reduces delirium incidence and its duration in medico-surgical ICU patients with no effect on mortality rate and ICU LOS.