The objective of this study is to elucidate the association between high-arsenic artesian well water and cancers in endemic area of blackfoot disease, a unique peripheral vascular disease related to continuous arsenic exposure. As compared with the general population in Taiwan, both the standardized mortality ratio (SMR) and cumulative mortality rate were significantly high in blackfoot disease-endemic areas for cancers of bladder, kidney, skin, lung, liver, and colon. The SMRs for cancers of bladder, kidney, skin, lung, liver, and colon were 1100, 772, 534, 320, 170, and 160, respectively, for males, and 2009, 1119, 652, 413, 229, and 168, respectively, for females. A dose-response relationship was observed between SMRs of the cancers and blackfoot disease prevalence rate of the villages and townships in the endemic areas. SMRs of cancers were greater in villages where only artesian wells were used as the drinking water source than in villages using both artesian and shallow wells, and even greater than in villages using shallow wells only.