The present work explains a coupled CFD-thermoregulation model developed for the air ventilation clothing to predicts its performance. The coupled model predicts heat transfer coefficients for various torso segments of the human body using a 3D CFD model and then uses these heat transfer coefficients as input parameters to the JOS-3 thermoregulation model to determine physiological responses such as skin and core temperatures, by numerically simulating heat exchange within the body and that between the body and the environment. Based on local boundary conditions which represent both ambient conditions and individual characteristics, the coupled model can be used to analyze local and overall thermal comfort. The coupled model can analyze the performance of air ventilation clothing without conducting human trials or manikin experiments, which saves time, effort, and resources. Human trials are conducted, and the developed coupled model is validated with experimental data under different scenarios. It is observed that the developed coupled model can provide reliable value and trend of the human physiological responses in terms of mean skin, mean torso and core temperatures. Further, the developed and validated coupled model is used to analyze performance of the air ventilation clothing under different climatic conditions and activity levels under three different clothing setting [control with fan OFF (CON), low air flow rate (LV) and high air flow rate (HV)]. Maximum reductions in the mean torso, mean skin, and core temperatures, in case of HV is found to be 3.4 °C, 1.3 °C, and 0.3 °C, respectively, as compared to the CON case in all set of climate conditions and activity level studied in present work. At a moderate activity level (3.2 MET), the air ventilation clothing with HV can reduce core temperature by 0.2 °C in temperate (27 °C, 50%), hot-dry (36 °C, 30%), and hot-humid (38 °C, 45%) climate conditions. Further, it is observed that in case of an intermittent working situation (environmental condition: 45 °C, 10% RH), overall working duration can be increased by 18 min in case of HV as compared to the CON case.