To evaluate the efficacy of ranibizumab in the treatment of choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome. Patients enrolled in the ranibizumab group received a monthly intravitreal injection of 0.5 mg of ranibizumab. Patients in the photodynamic therapy (PDT) group received a quarterly dosing of intravenous verteporfin coupled with PDT. Mean change in ETDRS visual acuity at 1 year was 19.6 letters in the ranibizumab group versus 21 letters in the PDT group. All patients in the PDT group required rescue ranibizumab therapy. Four of five patients (80%) in the ranibizumab group and one of two patients (50%) in the PDT group showed a greater than 15 letter gain at 1 year. Ranibizumab appears to be a safe and effective treatment option for choroidal neovascularization secondary to the presumed ocular histoplasmosis syndrome.