PURPOSE. To examine whether baseline retinal vascular caliber predicts visual response to intravitreal ranibizumab injections in patients with neovascular age-related macular degeneration (AMD). METHODS. In this prospective cohort study, patients with neovascular AMD received three monthly intravitreal injections of ranibizumab, followed by as needed dosing up to 1 year. Retinal vascular caliber was measured from digital fundus photographs at baseline and summarized as central retinal artery equivalent (CRAE) and venular equivalent (CRVE), representing average caliber of arterioles and venules, respectively. Visual outcome at 12 months was assessed and the relation to baseline retinal vascular caliber was determined. RESULTS. A total of 88 eyes were analyzed at baseline. After accounting for age, sex, size of choroidal neovascularization, and number of injections, patients who deteriorated in visual acuity at 12 months had significantly larger baseline CRVE, 243.10 μm (95% confidence interval [CI], 227.01-259.19), compared with those who were stable, 214.30 μm (95% CI, 205.79-222.81) and those who improved, 215.26 μm (95% CI, 204.69-225.84; P = 0.007). Baseline CRAE did not differ significantly from eyes whose vision deteriorated, 150.12 μm (95% CI, 140.67-159.57), compared with those remaining stable, 143.64 μm (95% CI, 138.64-148.63), or gaining vision 142.92 μm (95% CI, 136.71-149.13; P = 0.69). CONCLUSIONS. In eyes with neovascular AMD treated with intravitreal ranibizumab, larger baseline retinal venular caliber was significantly associated with a poorer response to treatment, possibly reflecting increased disease severity.