PURPOSE: To evaluate the effect of a sequentially combined triple therapy on intractable diabetic macular edema (DME). DESIGN: Prospective, interventional case series. METHODS: Twenty-four eyes from 24 subjects, diagnosed with intractable DME of nontractional origin, were subjected to vitrectomy. Intravitreal triamcinolone acetonide injection and macular laser photocoagulation were conducted sequentially at one and 14 days after vitrectomy. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were recorded before surgery and at three, six, and 12 months after triple therapy. 0 RESULTS: The mean (+/- standard deviation [SD]) logarithm of the minimum angle of resolution BCVAs before and three, six, and 12 months after the triple therapy were 0.88 +/- 0.37, 0.55 +/- 0.33, 0.56 +/- 0.27, and 0.48 +/- 0.28, respectively. The mean (+/- SD) CMTs before and three, six, and 12 months after the triple therapy were 514 +/- 187 mu m, 253 +/- 138 mu m, 219 +/- 95 mu m, and 197 +/- 91 mu m, respectively. The changes in both BCVA and CMT at three, six, and 12 months from baseline were statistically significant (P<.003). The major adverse events after triple therapy were development of nuclear sclerotic cataracts (eight among 12 phakic eyes) and elevation of intraocular pressure (eight among 24 eyes). CONCLUSIONS: The triple therapy may facilitate early recovery of vision and may improve the long-term outcomes in some patients with DME refractory to conventional monotherapy.