Protective clothing ensembles are worn by workers as a barrier to chemical and physical hazards, but can restrict heat loss and increase worker heat stress. The question of whether a respirator adds to heat stress or strain burden is a continuing concern among occupational health professionals. The purpose of this study was to determine if there are differences in heat stress or strain among the current Toxicological Agent Protective (TAP) ensemble and two ensemble variations used in demilitarization of chemical weapons. Four acclimatized adult males wore five ensembles in a balanced design while walking in a climatic chamber at a metabolic rate of about 170 W m-2. Heat stress (critical wet bulb globe temperature-WBGTcrit, evaporative resistance-Re,T,a, Clothing Adjustment Factor [CAF]) and heat strain (physiological strain index [PSI]) were compared against work clothes (WC) without respirator (a baseline ensemble); the current TAP apron over cloth coveralls with respirator (TAP+CA); the current TAP apron over cloth coveralls with respirator plus Tychem F® chemical barrier pants (TAP+CA+P); and Tychem F® Coveralls over cloth coveralls with respirator (VB+CA). A no-respirator comparison with the Tychem F coveralls (VB+CA-noR) was added to evaluate the contribution of a full-face negative pressure air-purifying respirator to heat stress. A progressive heat stress protocol was used to determine WBGTcrit, Re,T,a, CAF, and PSI. The results (WBGTcrit [°C-WBGT], Re,T,a [kPa m2 W-1], and PSI) were WC (35.5, 0.0112, 2.0), TAP (31.6, 0.0175, 1.8), TAP+P (27.7, 0.0240, 1.9), VB+CA (25.9, 0.0287, 1.8), and VB+CA-noR (26.2, 0.0293, 1.8). Mixed effects ANOVA was used to assess ensemble effects. Tukey's test was used to determine where significant differences occurred. WBGTcrit was the WBGT at the upper limit of thermal balance. Re,T,a increased while WBGTcrit progressively decreased going from WC to TAP+CA to TAP+CA+P to VB+CA. WBGTcrit was different between Work Clothes and TAP+CA and between WC and TAP+CA and the other ensembles. Re,T,a was different among all ensembles, except no differences in WBGTcrit and Re,T,a were observed between the presence and absence of a respirator with VB+CA. There were no differences among all ensembles for rectal temperature, heart rate, and PSI. Based on both WBGTcrit and Re,T,a, there were significant increases in heat stress going from WC to TAP+CA to TAP+CA+P to VB+CA. No differences in WBGTcrit, Re,T,a, and PSI were found for the presence or absence of a respirator, indicating no additional heat stress or strain burden. CAF is the WC WBGTcrit minus the ensemble WBGTcrit.. The recommended clothing adjustment factors (CAFs) are 0°C-WBGT for WC, 4 °C-WBGT for TAP+CA, 8 °C-WBGT for TAP+CA+P and 10 °C-WBGT for VB+CA. As vapor-barrier ensembles are sensitive to humidity, adding 2 °C-WBGT to VA+CA for a CAF of 12 °C-WBGT is recommended. This implicates the type of protective clothing ensemble worn will play a much bigger role in workplace heat stress effects and risk than the wear of a respirator.