OBJECTIVES: The purpose of this study was to investigate the effect of 16 weeks of Bikram yoga on perceived stress, self-efficacy and health related quality of life (HRQoL) in sedentary, stressed adults. DESIGN: 16 week, parallel-arm, randomised controlled trial with flexible dosing. METHODS: Physically inactive, stressed adults (37.2+/-10.8 years) were randomised to Bikram yoga (three to five classes per week) or control (no treatment) group for 16 weeks. Outcome measures, collected via self-report, included perceived stress, general self-efficacy, and HRQoL. Outcomes were assessed at baseline, midpoint and completion. RESULTS: Individuals were randomised to the experimental (n=29) or control group (n=34). Average attendance in the experimental group was 27+/-18 classes. Repeated measure analyses of variance (intention-to-treat) demonstrated significantly improved perceived stress (p=0.003, partial eta(2)=0.109), general self-efficacy (p=0.034, partial eta(2)=0.056), and the general health (p=0.034, partial eta(2)=0.058) and energy/fatigue (p=0.019, partial eta(2)=0.066) domains of HRQoL in the experimental group versus the control group. Attendance was significantly associated with reductions in perceived stress, and an increase in several domains of HRQoL. CONCLUSIONS: 16 weeks of Bikram yoga significantly improved perceived stress, general self-efficacy and HRQoL in sedentary, stressed adults. Future research should consider ways to optimise adherence, and should investigate effects of Bikram yoga intervention in other populations at risk for stress-related illness. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12616000867493. Registered 04 July 2016. URL: http://www.anzctr.org.au/ACTRN12616000867493.aspx.