The vasomotor response to cold may compromise the capacity for microclimate cooling (MCC) to reduce thermoregulatory strain. This study examined the hypothesis that intermittent, regional MCC (IRC) would abate this response and improve heat loss when compared with constant MCC (CC) during exercise heat stress. In addition, the relative effectiveness of four different IRC regimens was compared. Five heat-acclimated men attempted six experimental trials of treadmill walking (~225 W/m²) in a warm climate (dry bulb temperature = 30°C, dewpoint temperature = 11°C) while wearing chemical protective clothing (insulation = 2.1; moisture permeability = 0.32) with a water-perfused (21°C) cooling undergarment. The six trials conducted were CC (continuous perfusion) of 72% body surface area (BSA), two IRC regimens cooling 36% BSA by using 2:2 (IRC₁) or 4:4 (IRC₂) min on-off perfusion ratios, two IRC regimens cooling 18% BSA by using 1:3 (IRC₃) or 2:6 (IRC₄) min on-off perfusion ratios, and a no cooling (NC) control. Compared with NC, CC significantly reduced changes in rectal temperature (~1.2°C) and heart rate (~60 beats/min) (P < 0.05). The four IRC regimens all provided a similar reduction in exercise heat strain and were 164-215% more efficient than CC because of greater heat flux over a smaller BSA. These findings indicate that the IRC approach to MCC is a more efficient means of cooling when compared with CC paradigms and can improve MCC capacity by reducing power requirements.