Objective:The intervention of yoga has been shown to improve autonomic conditioning in humans and better adaptability to orthostatic challenges. Similarly, slow breathing at 0.1 Hz akin to pranayama also increases baroreflex sensitivity (BRS). Hence, we intended to investigate whether yoga practitioners have different autonomic responses at rest,during slow deep breathingas well as during 6° head down tilt (HDT) compared to naive group individuals.Aim:The aim of the study was to evaluate the acute effects of slow breathing on cardiovascular variability during HDT in yoga practitioners compared to yoga-naïve individuals.Settings and Design:This was a comparative study with repeated measures design conducted in Autonomic Function Test lab of the Department of Physiology, All India Institute of Medical Sciences, New Delhi, India.Materials and Methods:Time domain and frequency domain parameters of heart rate variability, blood pressure variability (BPV), and BRS were evaluated during 6° HDT and slow breathing at 0.1 Hz on forty yoga-naïve individuals and forty yoga practitioners with an average age of 31.08 ± 7.31 years and 29.93 ± 7.57 years, respectively. All of the participants were healthy.Statistical Analysis Used:General Linear Mixed Model ANOVA was applied with yoga experience as a between-group factor in repeated measures. Independent sample t-test was applied for between group comparison of respiratory rate, demographic, and anthropometric data. P <0.05 is considered statistically significant.Results:Between-group comparison during HDT with spontaneous breathing has shown a significantly lower heart rate (P = 0.004) with higher RR interval (RRI) (P = 0.002) and pNN50% (P = 0.019) in yoga practitioners. The sequence BRS (P < 0.0001) and α low frequency (LF) of spectral BRS (P = 0.035) were also significantly higher in the yoga group compared to the naïve group. Similarly, during HDT with slow breathing, the heart rate was lower (P = 0.01); with higher RRI (P = 0.009); pNN50% (P = 0.048). Standard deviation of successive RR interval difference of systolic BPV was lower (P = 0.024) with higher sequence BRS (P = 0.001) and α LF of spectral BRS (P = 0.002) in yoga group than naïve group.Conclusion:The yoga experienced individuals exhibit higher resting parasympathetic activity, lower systolic BPV, and higher BRS than naïve to yoga individuals. It is inferred from the findings that yoga practitioners were better adapted to transient cephalad fluid shift that happens during 6° HDT. Furthermore, acute slow breathing during 6° HDT reduced the systolic blood pressure in all the participants suggesting the beneficial role of slow breathing during exposure to extreme conditions such as microgravity which might help in the prevention of adverse effects of cephalad fluid shift during long-term weightlessness and maintain the astronaut health. Future mechanistic studies with active yoga intervention are necessary to understand the adaptive mechanisms involving central and vascular modulations contributing to either attenuation or accentuation of the cardiovagal baroreflex during HDT and slow breathing in healthy individuals.