OBJECTIVE: To evaluate the role of heart rate variability (HRV) in predicting pre-operative severity of appendicitis. METHODS: In this cross-sectional study, 171 cases of acute appendicitis who underwent appendectomy were enrolled. Pre-anesthetic pulse rate of included patients were documented while the severity of appendicitis was determined by intra-operative evidences reported by two independent surgeons. Demographic characteristics, laboratory variables, and Alvarado criteria were recorded. RESULTS: The mean age of patients was 28.75+/-4.21 years; 54% were men. HRV negatively associated the severity of appendix inflammation. A positive association was found between HRV and omental wrapping and Alvarado score (p<0.01). The receiver operating characteristic (ROC) curve analysis demonstrated that HRV could differentiate simple and complicated appendicitis with a sensitivity of 78.5% and specificity of 97.2%. CONCLUSION: The present findings revealed that HRV may predict the pre-operative severity of appendicitis and help differentiate simple and complicated appendicitis.