Delirium is the most common problem in patients in intensive care units. Prevention of delirium is more important than treatment. The aim of this study is to determine the effect of the NICE-adjusted multifactorial intervention to prevent delirium in open heart surgery patients. Methods: This study is a quasi-experimental study on 88 patients (In each group, 44 patients) undergoing open heart surgery in the intensive care unit of Imam Khomeini Hospital, Tehran. Subjects received usual care group, only the incidence of delirium were studied. So that patients in the two groups of second to fifth postoperative day, twice a day by the researcher, and CAM-ICU questionnaire were followed. After completion of the sampling in this group, in the intervention group also examined incidence of delirium was conducted in the same manner except that multifactorial interventions based on the intervention of NICE modified by the researcher on the second day to fifth implementation and intervention on each turn, their implementation was followed. As well as to check the quality of sleep and pain in the intervention group of CPOT and Pittsburgh Sleep assessment tools were used. Data analysis was done using the SPSS software, version 16. A T-test, a chi-square test, and a Fisher’s exact test were also carried out. Results: The incidence of delirium in the control group was 42.5%; and in the intervention group, it was 22.5%. The result showed the incidence of delirium in open heart surgery hospitalized patients after multifactorial intervention based on adjusted NICE guidelines has been significantly reduced. Conclusion: The NICE-adjusted multifactorial intervention guidelines for the prevention of delirium in cardiac surgery patients significantly reduced the incidence of delirium in these patients. So, using this method as an alternative comprehensive and reliable in preventing delirium in hospitalized patients in the ward heart surgery is recommended.