Using effectiveness data from a recent systematic review and cost data from programme implementers and World Health Organization (WHO) databases, we conducted a cost-effectiveness analysis to compare non-piped in source- (dug well, borehole and communal stand post) and four types of household- (chlorination, filtration, solar disinfection, flocculation/disinfection) based interventions to improve the microbial quality of water for preventing diarrhoeal disease. Results are reported for two WHO epidemiological sub-regions, Afr-E (sub-Saharan African countries with very high adult and child mortality) and Sear-D (South East Asian countries with high adult and child mortality) at 50% intervention coverage. Measured against international benchmarks, source- and household-based interventions were generally cost effective or highly cost effective even before the estimated saving in health costs that would offset the cost of implementation. Household-based chlorination was the most cost-effective where resources are limited; household filtration yields additional health gains at higher budget levels. Flocculation/disinfection was strongly dominated by all other interventions; solar disinfection was weakly dominated by chlorination. In addition to cost-effectiveness, choices among water quality interventions must be guided by local conditions, user preferences, potential for cost recovery from beneficiaries and other factors.