PurposeTo explore the application effect of a comprehensive intervention program for postoperative delirium (POD) prevention. DesignDescriptive and comparative study. MethodsThis study included 82 elderly patients who underwent cardiac surgery as the control group to receive routine perioperative care. Seventy seven elderly patients who underwent cardiac surgery were selected as the observation group and received a comprehensive intervention program for POD prevention. This study further compared the length of stay in the hospital, nutritional status, pain score, and sleep quality between the two groups after intervention. FindingsThe postoperative length of stay in the hospital of the observation group was shorter than that of the control group (12.60 ± 2.97 vs 17.30 ± 7.10), and the incidence of POD was lower than that of the latter group (24.68% vs 47.56%, X2 = 8.976, P = .003). The pain scores of the observation group were lower than those of the control group (F = 195.381, P < .001). There was significant difference that the sleep quality score of the observation group was higher than that of the control group (F = 219.20, P < .001). The levels of albumin and hemoglobin in the observation group were higher than those in the control group (54.38 ± 5.87 vs 38.40 ± 3.11; 124.64 ± 13.18 vs 109.00 ± 10.20). The observation group had shorter mechanical ventilation duration, intensive care unit stay, and lower total hospital expenses compared with the control group (P < .05). ConclusionsThe comprehensive intervention program for POD prevention based on evidence-based medicine has a positive effect. In addition, it can also improve patients' pain, sleep quality, and nutritional status.