Post reperfusion syndrome (PRS) is a relatively common and life-threatening complication during orthotopic liver transplantation (OLT). It is associated with poor patient and transplanted liver outcomes. This study aimed to compare the risk factors of PRS during OLT. Clinical-epidemiological observational retrospective study. We gathered the records of patients who underwent OLT in 3 years, from May 22, 2016, to May 22, 2019, in Namazi and Bu-Ali Sina organ transplantation hospitals. In this study, we assessed 1182 patients who underwent OLT. Patients were divided into two groups based on the presence or absence of PRS. Diagnosing the predictors of PRS was the primary outcome of this study. Results showed that age > 60 years, Child-Pugh scores C, higher Model End Stage liver disease score, and preoperative sodium < 130 mmol/l (parameters of the liver recipient), increase in cold ischemic time (the donors' parameters), and the classical technique (the surgical parameters) were the strong predictors of PRS. The results indicated that underlying liver disease was not the predictor of PRS in the presence of other risk factors; therefore, clinicians have to consider these risk factors in patients undergoing OLT.