AIMS: To assess the clinical effectiveness of pegaptanib sodium and ranibizumab for neovascular age-related macular degeneration (AMD). METHODS: A systematic review of randomised controlled trials (RCTs) identified through searching 12 electronic databases, bibliographies and consultation with experts and manufacturers. RCTs were eligible if they assessed the effects of pegaptanib or ranibizumab with best supportive care, sham injection or photodynamic therapy (PDT) on patients with subfoveal choroidal neovascularisation associated with wet AMD and examined outcomes including visual acuity and adverse events. RESULTS: Three RCTs of ranibizumab (MARINA, ANCHOR, FOCUS) and two of pegaptanib (VISION study) met the inclusion criteria. The RCTs included patients with different lesion types. The studies showed statistically significant benefit on different measures of visual acuity for patients receiving pegaptanib, ranibizumab or ranibizumab with PDT compared to control (sham injection, PDT or sham injection with PDT) after 12 months. These differences appeared to be clinically significant. Although adverse events were common among those receiving pegaptanib or ranibizumab, they were considered mild to moderate in nature. Meta-analysis of ranibizumab trials and indirect comparison of the two drugs were not possible due to differences in the study populations' lesion types. However, results from the RCTs of ranibizumab tended to show a greater effect on visual acuity than results from the RCT of pegaptanib. CONCLUSIONS: Pegaptanib and ranibizumab appear to slow or stop the progression of neovascular AMD. Uncertainty remains over the relative benefits of pegaptanib compared with ranibizumab and other unlicensed drugs (eg, Avastin), due to the nature of the evidence. Head-to-head RCTs and economic evaluations comparing these alternatives are needed.