Vernal keratoconjunctivitis (VKC) is an allergic eye disease and an important cause of hospital referral among children in Africa and Asia. Hospital-based studies have suggested a role for parasites in its pathogenesis. To determine the prevalence and risk factors for VKC in Central Africa, we conducted a nested population-based case control study in Rwanda, involving randomly selected primary schools from different environments (rural/urban) and climate. A prevalence of VKC of 4.0% (95% confidence interval 3.3–4.7%) was found among 3,041 children studied (participation rate 94.7%). The intestinal parasitic burden was not related to VKC. Besides hot dry climate (odds ratio [OR] = 1.5, P = 0.05) and male gender (OR = 1.7, P = 0.005), multivariate analysis identified higher economic status as a risk for VKC (OR = 1.4, P = 0.005). The effect on VKC of higher economic status appears not to act through differences in parasitic intestinal load.