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Background. Nursing staff suffer from various level of stress and burnout. We aimed to assess the effect of 12 weeks of structured yoga on stress and the professional quality of life among nursing staff. Design and method. An open-label, phase-II randomized clinical trial was undertaken considering a sample size of convenience was done. In service nursing staff were randomized (1:1) to intervention group and wait-list control group. Primary outcome was perceived stress which was measured by Perceived Stress Scale (PSS). Secondary measures were professional quality measured by Professional Quality of Life (ProQOL) scale, blood pressure, serum cortisol, and high-sensitive C-reactive protein. Both the per-protocol and intention to treat analysis was done. Results. Total 113 participants were allocated to intervention group (n = 58, mean = 35 years, SD = 7.9 years) and wait-list control group (n = 55, mean = 32.5 years, SD = 6.8 years). After 12 weeks, 19 participants of intervention group and 32 participants of wait-list control group were included in the per-protocol analysis. Follow-up mean PSS score was 15.4 (95% CI 12.6-18.2, SD 5.8) in intervention group, 20.7 (95% CI 19.7-21.7, SD 2.8) in wait-list control group (p-value < 0.0001). The other parameters didn’t differ between the groups and from baseline to end line too. Conclusions and relevance. The finding showed supervised structured yoga may be efficacious to reduce stress. Studies with larger sample size are needed to confirm the findings. Trial registration. It was approved by the Institute Ethics Committee (Reference no: IECPG-543/20.12.2017, RT-57/31.01.2018) and was registered prospectively in the Clinical Trial Registry of India prospectively (No. CTRI/2018/02/012206).