Background: To determine if primary intravitreal injection of triamcinolone acetonide (TA) plus grid laser photocoagulation (GLP) is effective in treating cystoid diabetic macular edema (DME). Methods: Prospective comparative non-randomized clinical trial. Fourteen eyes (14 patients) diagnosed with cystoid DME were treated with GLP according to the Early Treatment Diabetic Retinopathy Study (ETDRS) guidelines, plus an intravitreal injection of 4 mg of TA. A matched control group (16 eyes [16 patients]) treated with GLP was selected retrospectively from our medical records. Best-corrected visual acuity (BCVA), and quantitative change in optical coherence tomography (OCT) macular thickness were assessed. Results: Mean follow up was 14.9 months (12 to 19 months). In 3 (21.4%) eyes BCVA increased > 2 ETDRS lines, in 5 (35.7%) eyes BCVA remained the same, and BCVA decreased >2 ETDRS lines in 6 (42.8%) eyes. Central macular thickness, as measured by OCT, decreased a mean of 106.2 μm (30.2%). The difference with the control group was not statistically significant (P=.2). Four (28.5%) eyes developed an increased in intraocular pressure in our study group. Conclusions: Although all of our patients showed an improvement of cystoid DME by means of OCT and fluorescein angiography, 42.8% (6 eyes) lost 2 or more lines in BCVA with primary intravitreal injection of TA plus GLP. Primary intravitreal injection of TA plus GLP may not be effective for cystoid DME at 12-months. © 2010 Sociedad Española de Oftalmologia.