AIM: To evaluate the efficacy of prophylactic administration of topical non-steroidal anti-inflammatory drugs (NSAIDs) on macular edema following cataract surgery in diabetic patients, and to compare between types of NSAIDs (ketorolac tromethamine 0.4% and nepafenac 0.1%). METHODS: Group 1 (control) received artificial tears substitute as a placebo group, group 2 (nepafenac) received topical nepafenac 0.1%, and group 3 (ketorolac) received topical ketorolac tromethamine 0.4%. Patients were examined postoperatively after completing one week, one month, two months and three months' intervals for evaluating cystoid macular edema (CME) development. The main study outcomes were achieving the best corrected visual acuity (BCVA) and change in the central macular thickness (CMT) measured with optical coherence topography (OCT). RESULTS: Eighty eyes of 76 patients were included in this study. BCVA showed a statistically significant difference at the third month postoperative follow up between the control group and the NSAIDs groups (P=0.04). There was an increase in the CMT in all cases starting from postoperative first week until third month. CMT showed a statistically significant difference between control group and NSAIDs groups from postoperative first month until third month (P=0.008, 0.027, 0.004). There was no statistically significant difference between nepafenac and ketorolac groups in BCVA and OCT CMT. CONCLUSION: Prophylactic preoperative and postoperative NSAIDs may have a role in reducing the frequency and severity of CME in diabetic eyes following cataract surgery.