Previous studies have indicated the association between C2 rs547154 polymorphism and polypoidal choroidal vasculopathy (PCV) risk, while the results are controversial and inconsistent. Herein, we perform a meta-analysis to gain a precise estimation of the association using 5 eligible studies involving 4076 subjects, of which 1220 were PCV cases, 1073 were age-related macular degeneration (AMD) cases and 1783 were controls. Allelic frequencies of C2 rs547154 polymorphism between PCV and AMD were also compared. Both crude and adjusted odds ratios (OR) with their 95% confidence interval (CI) were included to assess the strength of the association. The pooled OR in random-effect model for allele T versus G was 0.64 (95% CI, 0.52-0.80; p < 0.0001), for genotype TG versus GG was 0.65 (95% CI, 0.52-0.83; p, 0.0004), and for genotype TT + TG versus GG was 0.64 (95% CI, 0.51-0.80; p, 0.0002). No difference in allelic frequency was observed between PCV and AMD (OR, 0.86; 95% CI, 0.64-1.16; p, 0.32). Sensitivity analysis proved the robustness of our data. No significant ethnic divergence was suggested by subgroup analysis, and no publication bias was detected via Egger's test. In conclusion, our data indicate that C2 rs547154 polymorphism plays a protective role in the development of PCV.