Medical error is one of the most critical challenges facing medical services. They pose a substantial threat to patient safety, and their costs draw attention from policymakers, health care planners and researchers. We aim to make a realistic estimation of medical error incidence and related costs and identify factors influencing this incidence in Iranian hospitals. In the first phase of this multi-method study, through two reviews of systematic reviews and a meta-analysis, we will estimate the incidence of medical errors and the strategies to reduce them. We will extract available data among 41 hospitals supervised by the East Azerbaijan University in the second phase. We will also develop a model and use a Delphi method to predict medical errors incidence and calibrate our model output using the Monte Carlo simulation. We will compare this estimation with the incidence rate based on meta-analysis results from the first phase. In the third phase, we will investigate the relationship between several factors potentially influencing medical error incidence. In the fourth phase, we will estimate costs associated with medical errors by conducting a patient records review and matching those with claims related to medical errors. In the fifth phase, we will present a policy brief related to strategies for medical errors and associated costs reduction in Iran. Our findings could benefit Iranian and policymakers in other countries to reduce medical errors and associated costs.