ABO blood groups have been associated with various disease phenotypes, particularly cardiovascular diseases 1, 2. Heart rate variability (HRV) signal is an important tool for studying the autonomic nervous system3. Decreased HRV is a dependable predictor of future cardiovascular disease 4, 5. This study was designed to find out the association between different A, B, O blood groups and HRV in young adults. This cross sectional study included 120 volunteered healthy students. Institutional medical ethical committee approval was obtained and written informed consent was taken from all the subjects. Subjects were grouped into A, B, AB and O based on their blood groups determined by slide agglutination test. HRV was analyzed by measuring the R-R intervals using HRV soft 1.1 Version. Time domain and frequency domain method was used to analyze HRV during normal breathing at rest for five minutes. HRV was also analyzed during deep breathing for one minute using time domain method. In time domain method, root of the mean of the squared successive R-R interval differences (RMSSD), and standard deviation of normal RR intervals (SDNN) in milliseconds were analyzed and in frequency domain method low frequency (LFnu) components (0.04 to 0.15Hz) and the high frequency (HFnu) components (0.15 to 0.4 Hz) in normalized units were measured. The data were expressed as Mean ± standard deviation. Results were analyzed statistically by ANOVA (analysis of variance), and P-value <0.05 was taken as significant. Analysis of HRV during deep breathing showed a statistically significant (P value=0.04) increase in SDNN value in O blood group subjects (75.67 ± 12) compared to A, B and AB blood groups subjects (72.03 ± 13, 73.21± 12, 72.49 ± 14). However, HRV analysis by time domain during normal breathing in different blood groups A, B, AB and O did not show any statistical significant difference in SDNN value (58.07 ± 15, 65.54 ± 21, 66.24 ± 19, and 70.95 ± 15; P value=0.44) and RMSSD value (51.30 ± 20, 51.97 ± 17, 59.36 ± 20 and 59.79 ±16; P value=0.738). Further, HRV analysis by frequency domain method during normal breathing, also did not show any statistically significant (P value= 0.633) difference among different A, B, AB and O blood groups in LFnu (53.65 ±17, 52.97 ±23, 59.93 ± 23 and 51.69 ±19) and HFnu value (46.35 ±17, 47.03 ± 23, 40.07 ± 23 and 48.31 ± 19). In conclusion this study shows, a better HRV in O blood group individuals during deep breathing. This may offer some protection from cardiovascular diseases but blood group alone may not compensate for other factors that are linked to the cardiovascular diseases. Other blood group individuals may need to adopt more preventive measure.