AIM: To compare the anatomical and functional outcomes of combined phacoemulsification with intravitreal dexamethasone implant (DEX-I) versus anti-vascular endothelial growth factor (VEGF) injections in patients with diabetic macular edema (DME) and visually significant cataract. METHODS: This nonrandomized, retrospective analysis included 54 eyes undergoing phacoemulsification with DEX-I (DEX-I group) and 47 eyes receiving anti-VEGF injections (anti-VEGF group). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were measured preoperatively and postoperatively at 1 and 3mo. RESULTS: The two groups had comparable baseline characteristics, with similar age (DEX-I: 66.83±7.27y; anti-VEGF: 66.81±6.79y) and gender distribution (51.9% vs 59.6% males). Both groups showed significant BCVA improvement at 1 and 3mo, with no significant intergroup differences. CMT reduction was significantly greater in the DEX-I group at 3mo (25.03% vs 14.07%; P=0.049), particularly in recalcitrant eyes (25.09% vs 11.10%; P=0.007). Postoperative intraocular pressure (IOP)>21 mm Hg was observed in 14.8% of DEX-I eyes and 4.25% of anti-VEGF eyes (P=0.08), normalizing by 3mo. DEX-I required no reinjection, while 29.79% of anti-VEGF eyes needed a fourth dose at 3mo. Complications were minimal, with one posterior capsular injury in the DEX-I group. CONCLUSION: Combined phacoemulsification with intravitreal DEX-I offers superior CMT reduction and comparable visual acuity improvement to anti-VEGF injections in DME, with fewer required treatments. It is an effective strategy for managing cataract with DME, offering benefits, especially for recalcitrant cases. Both therapies have favourable safety profiles, but further long-term studies are needed for clinical guidance.