Abstract Background Oral cholera vaccine (OCV) and incremental improvements in household water, sanitation, and hygiene (WASH) within cholera-endemic areas can reduce cholera risk. However, we lack empiric evaluation of their combined impact. Methods We evaluated a cluster-randomized, placebo-controlled trial of OCV (Shanchol) in Kolkata, India. The study population included 108 777 individuals, and 106 879 nonpregnant individuals >1 year of age were eligible to receive 2 doses of OCV or placebo. We measured cholera risk in all household members assigned to OCV vs placebo and in all members of households with “Better” vs “Not Better” WASH, where WASH was classified according to validated criteria. Protection was measured by Cox proportional hazard models. Results Residence in an OCV household was associated with protective effectiveness (PE) of 54% (95% CI, 42%–64%; P < .001) and was similar regardless of Better (PE, 57%; 95% CI, 26%–75%; P = .002) or Not Better (PE, 53%; 95% CI, 40%–64%; P < .001) household WASH. Better WASH household residence was associated with PE of 30% (95% CI, 5%–48%; P = .023) and was similar in OCV (PE, 24%; 95% CI, −26% to 54%; P = .293) and placebo (PE, 29%; 95% CI, −3% to 51%; P = .069) households. When assessed conjointly, residence in OCV households with Better WASH was associated with the greatest PE against cholera at 69% (95% CI, 49%–81%; P < .001). Conclusions These findings suggest that the combination of a vaccine policy and improved WASH reduces cholera risk more than either would alone, although the magnitude of either intervention was not affected by the other. Future randomized trials investigating OCV and WASH interventions separately and together are recommended to further understand the interaction between OCV and WASH.