ABSTRACT Objectives To determine the efficacy of a multicomponent nursing program to prevent delirium in critically ill patients. Methods Parallel controlled randomized clinical trial to prevent delirium in 81 critically ill patients: 41 in the control group and 40 in the intervention group (intervention: spatial and temporal guidance, visual stimulus, auditive stimulus, and family support). Participants were recruited from September 2017 to March 2018 in the university hospital Los Comuneros, Bucaramanga, Colombia. Clinical Trials record NCT03215745. Results The incidence of delirium was 5% in the intervention group and 24% in the control group. The relative risk was 0.20 (95% CI 0.05 to 0.88). The absolute risk reduction was 19.39% (95% CI 4.61 to 34.17) and the number needed to treat was 5 (95 CI % 3 to 26%). Conclusion The multicomponent nursing program is efficient to prevent delirium in critically ill patients.