PURPOSE To evaluate the benefit of pars plana vitrectomy (PPV) and removal of the internal limiting membrane (ILM) in eyes with diffuse diabetic macular edema refractory to laser photocoagulation. DESIGN Prospective, consecutive, interventional case series. METHODS Diabetic patients with biomicroscopic, angiographic, and tomographic evidence of diabetic macular edema persisting for at least 3 months after numerous sessions of macular photocoagulation were evaluated for inclusion. Patients with biomicroscopic evidence of epiretinal membrane or taut posterior hyaloid, previous vitreoretinal surgery, or active proliferative diabetic retinopathy were excluded. The main outcome measures were macular thickness, as measured by optical coherence tomography (OCT) and visual acuity (VA). RESULTS PPV with ILM removal was performed in 11 eyes of 10 patients (four men, six women; mean age = 58.2 years). Six-month follow-up data were available for 10 eyes (91%). At 6 months postoperatively, central macular thickness had improved by at least 20% in eight of 11 eyes (mean preoperative thickness of 421 mum compared with mean postoperative thickness of 188 mum; P = .007). Mean VA improved from 20/352 to 20/94 at 6 months (P = .002). By the most recent visit (range = 6-20 months postoperatively), VA had improved by at least 2 Snellen lines in 6 of 10 eyes treated with surgery alone. CONCLUSIONS The early results of this ongoing study suggest that PPV with ILM removal may provide anatomic and visual benefit in some eyes with chronic diabetic macular edema unresponsive or unamenable to additional laser photocoagulation.