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In recent years, personal cooling has aroused much attention because it can achieve both localized high-level thermal comfort and build energy savings. In this study, a novel hybrid personal cooling vest (PCV) incorporated with phase change materials (PCMs) and ventilation fans was developed, and its efficacy was investigated by human trials in a hot-humid climate chamber. Three generally accepted indices (thermal load, Q; thermal sensation, TS; and physiological strain index, PSI) and a new proposed index (cumulative heat storage, CHS) during human trials were comparatively studied between the two human trial groups, i.e., the PCV group (wearing the PCV) and the CON group (without PCV). Results found that TS, PSI, and CHS were significantly reduced by the PCV, which suggests that the PCV can significantly improve both the perceptual and physiological strain. In addition, a strong linear relationship (r² = 0.8407) was found between the proposed index of CHS with PSI, which indicates the applicability and reliability of CHS for assessing physiological heat strain.