Purpose To investigate homocysteine (Hcy) concentration in the blood plasma and the vitreous in patients with exudative age-related macular degeneration receiving intravitreal anti-vascular endothelial growth factor therapy. Methods Plasma Hcy and vitreous Hcy levels were analyzed in 73 exudative age-related macular degeneration patients (50.7% received pegaptanib 0.3 mg and 50.3% received ranibizumab 0.5 mg) and compared with 80 controls and 40 patients with idiopathic epiretinal membranes, respectively. Homocysteine concentration was measured by immunonephelometric particle test, and it was determined before and after antiangiogenic therapy. Results The mean Hcy concentrations (± SD) of blood plasma and vitreous were 13.0 ± 4.2 μmol/L and 1.00 ± 0.3 μmol/L in patients treated with pegaptanib; in ranibizumab group, they were 12.8 ± 2.5 μmol/L and 1.4 ± 0.6 μmol/L, respectively. The results of plasma and vitreous Hcy indicated statistically significant differences between exudative age-related macular degeneration patients and control groups (P = 0.03 and P = 0.02). After 6 months with both intravitreal therapies, the plasma and vitreous Hcy concentrations did not change significantly (P = 0.1). Conclusion Pegaptanib and ranibizumab did not increase the plasma or vitreous Hcy concentrations.