To evaluate the efficacy of sequential intravitreal triamcinolone acetonide (TA) injection followed by grid laser photocoagulation for treating diabetic macular edema (DME). Prospective, 3-armed, randomized clinical trial. One hundred eleven eyes of 111 patients with DME involving the fovea. Patients were randomized to grid laser photocoagulation (37 eyes), 4 mg of intravitreal TA (38 eyes), or 4 mg of intravitreal TA combined with sequential grid laser about 1 month later (36 eyes). Central foveal thickness (CFT) as measured by optical coherence tomography, logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), and side effect profiles. The 6-month results are reported. All patients completed 6 months' follow-up. Baseline mean (+/- standard deviation) CFTs were 385+/-100 microm, 396+/-91 microm, and 424+/-108 microm for the laser, intravitreal TA, and combined groups, respectively (P = 0.24). After treatment, significant CFT reductions were noted in both the intravitreal TA and combined groups at all follow-up visits (P<0.01) but not in the laser group. Mean CFT improved significantly to minimums of 267+/-75 microm and 256+/-73 microm for the intravitreal TA and combined groups, respectively, but the difference between the 3 groups was not significant at 6 months. The standardized change in macular thickening at 17 weeks was significantly greater in the combined group versus the intravitreal TA group (P = 0.007), suggesting that combined treatment might prolong the effects of intravitreal TA. Mean baseline logMAR BCVAs were 0.64+/-0.37, 0.72+/-0.34, and 0.69+/-0.34 in the laser, intravitreal TA, and combined groups, respectively (P = 0.67). Best-corrected visual acuity improved significantly at 4 and 9 weeks for the intravitreal TA group but did not change significantly in the other 2 groups. No significant difference in BCVA was observed between the 3 groups at any time point. Contrary to the results of a recent study, combined treatment of intravitreal TA plus grid laser did not yield better CFT reduction or BCVA improvement at 6 months than intravitreal TA alone. Grid laser alone was significantly worse than the 2 other treatment modalities.