PURPOSE: To evaluate the anatomic and visual results and complications of vitrectomy in eyes with diffuse refractory diabetic macular edema associated with a taut posterior hyaloid. METHODS: This prospective interventional case series was conducted on 25 eyes of 22 patients with diffuse refractory clinically significant diabetic macular edema, macular thickness greater than 250 mm on optic coherence tomography (OCT) and thickened posterior hyaloid. Best-corrected visual acuity (BCVA) and macular thickness measured by OCT were evaluated preoperatively and repeated 3 and 6 months postoperatively. Macular perfusion was evaluated by fluorescein angiography, pre- and six months postoperatively. RESULTS: Mean BCVA was 1.14±0.51 LogMAR, preoperatively which improved to 0.89±0.53 LogMAR six months postoperatively (P=0.005). Mean preoperative macular thickness was 506±121.9 µm which decreased to 318±90.5 µm, six months postoperatively (P=0.001). CONCLUSION: Vitrectomy and removal of the posterior hyaloid membrane appears beneficial in eyes with diffuse diabetic macular edema unresponsive to laser therapy and a taut premacular posterior hyaloid.