Background: Bikram yoga may enhance health outcomes in healthy adults and those at risk for chronic disease, however, challenges remain in achieving optimal adherence to this practice. This study investigated factors influencing adherence to a 16-week Bikram yoga intervention in stressed and sedentary adults. Methods: Experimental group participants (n = 29) were instructed to attend 3–5 Bikram yoga classes weekly for 16 weeks. Baseline demographics, behaviours and health measures were investigated as predictors of adherence. Barriers were assessed via documentation of adverse events, and exit survey responses. Results: Participants (38.2 ± 10.1 years) were predominantly overweight-obese (83%), female (79%), and attended 27 ± 18 classes. Higher adherence was associated with older age (p = 0.094), less pain (p = 0.011), fewer physical limitations (p = 0.011), poorer blood lipid profile, and higher heart rate variability (HRV; total power, (p = 0.097)). In multi-variable analysis, three variables: age (β = 0.492, p = 0.006), HRV (β = 0.413, p = 0.021) and pain (β = 0.329, p = 0.048) remained predictors of adherence. Difficulty committing to the trial, lack of enjoyment and adverse events were barriers to adherence. Conclusions: These findings should be considered in the development of future Bikram yoga trials to facilitate higher levels of adherence, which may enhance health outcomes and inform community practice. Future trials should investigate and address additional barriers and facilitators of Bikram yoga practice.