Background. Infection with Onchocerca volvulus is associated with the prevalence of severe visual impairment and blindness. However, longitudinal studies of the incidence of blindness caused by onchocerciasis are scarce. Methods. The relationship, at the individual level, between infection with O. volvulus microfilariae and bilateral blindness was examined, by use of data collected, during the Onchocerciasis Control Programme in western Africa (OCP), from 2315 villages in 11 countries. The data were analyzed by Poisson maximum-likelihood techniques with adjustment for overdispersion. Results. A total of 297,756 persons were eligible for follow-up in the cohort, and, during 1971–2001, these persons accumulated 367,788 person-years of follow-up without blindness. A total of 673 bilateral cases of blindness occurred during this period; 29.7% were caused by onchocerciasis. After ivermectin therapy was introduced (during 1988–2001), only 19.6% of cases were caused by onchocerciasis. The incidence of blindness was significantly and positively associated with increasing microfilarial burden ( P < .001 ). Overall, female subjects had an ∼40% lower risk of becoming blind than did male subjects ( P < .001 ). After an initially high incidence of blindness at the beginning of the OCP, the rate of blindness from causes other than onchocerciasis remained approximately constant during follow-up. Conclusions. We demonstrate, in a comprehensive data set and in both sexes, a direct relationship between microfilarial load and the incidence of blindness.