BACKGROUND: There is a need to identify and evaluate an effective mitigation program for arsenic exposure from drinking water in Bangladesh. OBJECTIVE: We evaluated the effectiveness of a multifaceted mitigation program to reduce As exposure among 11,746 individuals in a prospective cohort study initiated in 2000 in Araihazar, Bangladesh, by interviewing participants and measuring changes in urinary As levels. METHODS: The interventions included a) person-to-person reporting of well test results and health education; b) well labeling and village-level health education; and c) installations of fifty deep, low-As community wells in villages with the highest As exposure. RESULTS: Two years after these interventions, 58% of the 6,512 participants with unsafe wells (As >=50 micrograms/L) at baseline had responded by switching to other wells. Well labeling and village-level health education was positively related to switching to safe wells (As < 50 micrograms/L) among participants with unsafe wells [rate ratio(RR)= 1.84; 95% confidence interval(CI), 1.60-2.11] and inversely related to any well switching among those with safe wells (RR = 0.80; 95% CI, 0.66-0.98). The urinary As level in participants who switched to a well identified as safe (< 50 micrograms As/L) dropped from an average of 375 micrograms As/g creatinine to 200 micrograms As/g creatinine, a 46% reduction toward the average urinary As content of 136 micrograms As/g creatinine for participants that used safe wells throughout. Urinary As reduction was positively related to educational attainment, body mass index, never-smoking, absence of skin lesions, and time since switching (p for trend< 0.05). CONCLUSIONS: Our study shows that testing of wells and informing households of the consequences of As exposure, combined with installation of deep community wells where most needed, can effectively address the continuing public health emergency from arsenic in drinking water in Bangladesh.