ABSTRACT The factors explaining variance in thermoneutral maximal oxygen uptake (O2max) adaptation to heat acclimation (HA) were evaluated, with consideration of HA programme parameters, biophysical variables and thermo-physiological responses. Seventy-one participants consented to perform iso-intensity training (range: 45%−55% O2max) in the heat (range: 30°C-38°C; 20%−60% relative humidity) on consecutive days (range: 5-days-14-days) for between 50-min and-90 min. The participants were evaluated for their thermoneutral O2max change pre-to-post HA. Participants’ whole-body sweat rate, heart rate, core temperature, perceived exertion and thermal sensation and plasma volume were measured, and changes in these responses across the programme determined. Partial least squares regression was used to explain variance in the change in O2max across the programme using 24 variables. Sixty-three percent of the participants increased O2max more than the test error, with a mean ± SD improvement of 2.6 ± 7.9%. A two-component model minimised the root mean squared error and explained the greatest variance (R2; 65%) in O2max change. Eight variables positively contributed (P < 0.05) to the model: exercise intensity (%O2max), ambient temperature, HA training days, total exposure time, baseline body mass, thermal sensation, whole-body mass losses and the number of days between the final day of HA and the post-testing day. Within the ranges evaluated, iso-intensity HA improved O2max 63% of the time, with intensity – and volume-based parameters, alongside sufficient delays in post-testing being important considerations for O2max maximisation. Monitoring of thermal sensation and body mass losses during the programme offers an accessible way to gauge the degree of potential adaptation.