AIM: To investigate the optimal anti-vascular endothelial growth factor (VEGF) treatment time in patients with diabetic macular edema (DME) scheduled for cataract surgery. METHODS: The study was designed to include 4 groups. Twenty-six eyes of 26 patients with diabetes but no retinopathy (DR; group 1), 17 eyes of 17 patients with DR but no DME (group 2), and 19 eyes of 19 patients with DME who received anti-VEGF therapy concurrently with cataract surgery (group 3), and 21 eyes of 21 patients who received anti-VEGF therapy for DME 1wk before cataract surgery (group 4). The patients’ best corrected visual acuity, intraocular pressure, central and mean macular thickness (CMT and MMT) values were noted on the day of surgery, postoperative day 1, week 1, and month 1. RESULTS: There was a significant increase of CMT after cataract surgery in groups 1, 2, and 3 (P<0.001, P=0.044, and P=0.034, respectively) but not in group 4 (P=0.948). The change in MMT was the same as CMT (P=0.009, P=0.006, P=0.011, and P=0.172, respectively). There was a higher increase in CMT and MMT ​​in group 2 compared to group 1 at the 1st month after surgery (P=0.002 and P=0.001, respectively). CONCLUSION: In eyes with DME undergoing cataract surgery, preoperative anti-VEGF treatment may be more effective than simultaneous intravitreal anti-VEGF with surgery.