Diarrhea is a leading cause of morbidity and mortality in people living with HIV (PLHIV) in Africa. The impact of a point-of-use water chlorination and storage intervention on diarrheal-disease risk in a population of HIV-infected women in Lagos, Nigeria was evaluated. A baseline survey was performed, followed by six weeks of baseline diarrhea surveillance consisting of weekly home visits, distribution of free water chlorination products and safe storage containers to project participants, and continued weekly home-based diarrhea surveillance for 15 additional weeks. To confirm use of the water chlorination product, during each home visit, stored water was tested for residual chlorine. About 187 women were enrolled. At baseline, 80% of women had access to improved water supplies and 95% had access to sanitation facilities. Following distribution of the intervention, water stored in participants' households was observed to have residual chlorine during 50-80% of home visits, a sign of adherence to recommended water-treatment practices. Diarrhea rates in project participants were 36% lower in the post-intervention period than during the baseline period (p=0.04). Diarrhea rates were 46% lower in the post-intervention period than the baseline period among project participants who were confirmed to have residual chlorine in stored water during 85% or more of home visits (p=0.04); there was no significant difference in diarrhea rates between baseline and post-intervention periods in participants confirmed to have residual chlorine in stored water during less than 85% of home visits. The percent change in diarrhea rates between baseline and post-intervention surveillance periods was statistically significant among non-users of prophylactic antibiotics (-62%, p=0.02) and among persons who used neither prophylactic antibiotics nor antiretroviral treatment (-46%, p=0.04). Point-of-use water treatment was associated with a reduced risk of diarrhea in PLHIV. Regular water treatment was required to achieve health benefits.