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Background and purpose: In recent years, Health System Reform Plan has been implemented in Iran to improve health care system. Medication costs, including medical prescriptions are major parts of the budget in this project. In the meantime, health insurance plays a significant role in providing these costs. This study aimed at evaluating the effect of Health System Reform Plan on the cost of medical prescriptions of patients with Health Insurance in selected public hospitals in Sari, Iran. Materials and methods: In this analytical study, inpatient prescriptions in two periods (2011-2013 and 2014-2015) were obtained from the health insurance organization. Data analysis was done in SPSS software. Results: The trend of cost changes was not significantly different in years before implementation of the Health System Reform Plan (2011-2013) and subsequent years. But, significant cost changes were seen in 2013-2016 (P= 0.311) and 2013-2014 (P=0.0204). Conclusion: Implementation of the Health System Reform Plan in 2014 increased the cost of medication prescriptions for health insurance, which continued in 2015, but in most hospitals the trend declined in 2016.