Blackfoot disease (BFD) is an endemic peripheral arterial disease confined to the southwestern coast of Taiwan. The cause of the disease has been ascribed to the high-arsenic artesian well water. The purpose of this study was to examine the possible association between the long-term exposure to artesian well water and the change in microvascular circulation in the absence of peripheral arterial insufficiency. A total of 45 men living in the BFD-hyperendemic villages and another 51 age- sex- body-mass index-matched men who lived in nonendemic villages nearby were recruited into this study. All subjects were free from peripheral vascular disease (resting ankle-brachial index > 1.00), clinical claudication, cigarette smoking, diabetes mellitus, hypertension, ischemic heart disease, cerebral infarction and obesity. Laser Doppler flowmetry was used to measure the peripheral microcirculation on the big toes both at 36 °C (basal perfusion, Pb) and after a hyperthermic test at 42 °C (Ph). The time required to reach Ph (T), and the average rate (R) of increase from Pb to Ph measured by (Ph -Pb)/T were also calculated. Results showed that those living in the BFD-hyperendemic area had a lower Pb [32.8 ± 6.0 perfusion units (PU) vs. 67.0 ± 4.3 PU, p < 0.001], a lower Ph (193.2 ± 13.6 vs. 231.1 ± 6.3 PU, p < 0.005), a longer T (3.04 ± 0.19 vs. 1.31 ± 0.08 min, p < 0.001) and a slower rate of increase from Pb to Ph (48.0 ± 4.8 vs. 76.2 ± 5.4 PU/min, p < 0.001). The results remained similar after excluding 13 subjects with minor arterial insufficiency defined as a postexercise ankle-brachial index < 0.90. We conclude that deficits in cutaneous microcirculation of the toes were demonstrated among seemingly normal subjects living in the BFD end