Background: Uneven body-surface thermal distribution is a manifestation of hypoperfusion and can be quantified by infrared thermography. Our aim was to investigate whether body-surface thermal inhomogeneity could accurately evaluate the severity of patients at risk of hypoperfusion. Methods: This was a prospective cohort study in which infrared thermography images were taken from unilateral legs of critically ill patients at high risk of hypoperfusion in a cardiac surgical intensive care unit. For each patient, five body-surface thermal inhomogeneity parameters, including standard deviation (SD), kurtosis, skewness, entropy, and low-temperature area rate (LTAR), were calculated. Demographic, clinical, and thermal characteristics of deceased and living patients were compared. The risk of mortality and capillary refill time (CRT) were chosen as the primary outcome and benchmarking parameter for hypoperfusion, respectively. The area under the receiver operating characteristic curve (AUROC) was used to evaluate predictive accuracy. Results: Three hundred seventy-three patients were included, and 55 (14.7%) died during hospital stay. Of inhomogeneity parameters, SD (0.738) and LTAR (0.768) had similar AUROC to CRT (0.757) for assessing mortality risk. Besides, there was a tendency for LTAR (1%-3%-7%) and SD (0.81°C-0.88°C-0.94°C) to increase in normotensive, hypotensive, and shock patients. These thermal parameters are associated with CRT, lactate, and blood pressure. The AUROC of a combined prediction incorporating three thermal inhomogeneity parameters (SD, kurtosis, and entropy) was considerably higher at 0.866. Conclusions: Body-surface thermal inhomogeneity provided a noninvasive and accurate assessment of the severity of critically ill patients at high risk of hypoperfusion.