Background: Medication errors and adverse drug events of high alert medication are one of the major problems in therapeutic system. The purpose of the present study was to investigate ύthe effect of clinical supervision model on high alert medication safety in intensive care units nurses. Materials and Methods: This was a quasi-experimental study conducted on 32 nurses of intensive care units. The researcher observed the administration of high alert drugs including heparin, warfarin, norepinephrine, dobutamine, and dopamine by nurses and recorded the scores of "the work in preventing medication errors," "the work in preventing adverse drug events," and "medication safety." Then, the researcher performed clinical supervision model and during performance of the model, the researcher reassessed the score of "the work in preventing medication errors", "The work in preventing adverse drug events" and "medication safety". Tool of data collection was "action plan of high alert medication safety" checklists (heparin, warfarin, norepinephrine, dobutamine, and dopamine checklists). Results: The result of the statistical trials showed that before and after applying the clinical supervision model, there was a statistically significant difference between the average scores of medication safety of heparin (15.7 vs 18.73), warfarin (11.08 vs 15.67), norepinephrine (14.60 vs 19.72), dobutamine (13.80 vs 19.30), and dopamine (14.25 vs 19.47). Conclusions: Based on the results of this study, it seems that administration of clinical supervision model in intensive care units can lead to improving the status of safety of high alert medication.