AIM: To determine the incidence and risk factors of retinopathy of prematurity (ROP) and the sensitivity of current screening criteria in a tertiary eye center in Tehran, Iran. METHODS: In a cross-sectional observational study, neonates weighing ≤2000 grams at birth or born <34wk gestational age (GA) and all other infants at risk of ROP admitted to the neonatal intensive care unit (NICU) or referred to our ROP clinic were investigated. The incidence of ROP and severe ROP (i.e. patients needing treatment) were determined. The associations between risk factors and the development and severity of ROP were assessed. We also examined the sensitivity of the current national screening guideline in Iran. RESULTS: Among 207 infants, the incidence of ROP and severe ROP was 33.3% and 11.1%, respectively. Mean GA and birth weight (BW) were significantly lower in ROP vs non-ROP infants (29±2wk vs 33±3wk, P<0.001; 1274±489 g vs 1916±550 g, P<0.001, respectively). Univariate analysis displayed significant association between ROP incidence and GA, BW, NICU admission period, blood transfusion, surfactant usage, sepsis, intraventricular hemorrhage and patent ductus arteriosus (P<0.05 for all). BW [relative risk (RR): 0.857 (0.711-0.873), P<0.001], GA [RR: 0.788 (0.711-0.873), P<0.001] and blood transfusion [RR: 1.888 (0.995-3.583), P=0.052] were independent ROP risk factors. The sensitivity of country-specific screening guidelines was 95.7% and 100% for overall and severe ROP detection, respectively. CONCLUSION: ROP incidence is relatively high in Iran. Identifying ROP risk factors results in more accurate screening and reduces the risk of irreversible vision loss. The ROP screening criteria utilized in Iran are efficient at the present time.