AIM: To compare the intravitreal binding activity of VEGF Trap with that of ranibizumab against vascular endothelial growth factor (VEGF) using a time-dependent and dose-dependent mathematical model. METHODS: Intravitreal half-lives and relative equimolar VEGF-binding activities of VEGF Trap and ranibizumab were incorporated into a first-order decay model. Time-dependent VEGF Trap activities (relative to ranibizumab) for different initial doses (0.5, 1.15, 2 and 4 mg) were calculated and plotted. RESULTS: Seventy-nine days after a single VEGF Trap (1.15 mg) injection, the intravitreal VEGF-binding activity would be comparable to ranibizumab at 30 days. After injection of 0.5, 2 and 4 mg VEGF Trap, the intravitreal VEGF-binding activities (comparable to ranibizumab at 30 days) would occur at 73, 83 and 87 days, respectively CONCLUSION: On the basis of this mathematical model, VEGF Trap maintains significant intravitreal VEGF-binding activity for 10-12 weeks after a single injection.