BACKGROUND: Hypertension (HTN) is the most prevalent non-infectious disease worldwide and can lead to mortality. This trial aimed to compare the effect of N-acetylcysteine (NAC) and angiotensin-converting enzyme inhibitors (ACEIs) on controlling blood pressure in hypertensive patients. METHODS: This cross-sectional clinical trial was conducted in Hajar Hospital, Shahrekord, Iran, in 2009. A sample of 126 patients with HTN was selected and randomly divided into 2 groups (group A and group B). First, group A was treated with ACEI alone and group B with ACEI + NAC for 2 months. Blood pressure of all patients was evaluated each week. After a 2 week period of washout, the drugs were changed. In the second period of the trial, group A was treated with ACEI + NAC and group B with NAC alone and their blood pressure was evaluated in the same manner as the previous period. The data were analyzed using SPSS. RESULTS: A significant reduction was observed in systolic and diastolic blood pressure of patients (P < 0.050). However, during both periods of the trial, the group receiving NAC + ACEI experienced a more significant reduction in blood pressure compared with the ACEI group (P < 0.050). CONCLUSION: NAC accompanied with ACEI decreased the patients' systolic and diastolic blood pressure significantly; however, ACEI alone did not have any significant effects on blood pressure. Systolic blood pressure decreased 7 mmHg on average and fluctuated during the trial