OBJECTIVE The present investigation was conducted to evaluate the effect of sildenafil citrate (Viagra, Pfizer Inc., New York, NY) on retinal blood vessel diameter. METHODS Double-blind randomized, placebo-controlled, cross-over study. METHODS Fifteen healthy male volunteers (mean age 39 years) received 100-mg doses of sildenafil or matching placebo on 2 separate days. Monochromatic fundus photography was obtained in one eye, and brachial artery blood pressure and intraocular pressure were measured at baseline, 1 hour, and 5 hours after dosing. The diameters of two major temporal veins and one artery were measured in a masked fashion from digitized photographic negatives. RESULTS In comparison with placebo, no statistically significant change in average venous diameter was observed for the superior (analysis of variance [ANOVA], P =.97), inferior retinal temporal vein (ANOVA, P =.73), or the retinal temporal artery (ANOVA, P =.89) after sildenafil treatment. In comparison to placebo, there was no significant difference in the percentage change from baseline in venous or arterial diameter at 1 or 5 hours after sildenafil. The power to detect a 6.5% change in retinal vascular diameter following sildenafil was approximately 80% (P =.05). CONCLUSIONS These data suggest that at the maximum therapeutic dose used clinically (100 mg), sildenafil does not have a significant effect on retinal vascular caliber.