Background: The increasing trend in animal bites and rabies in recent years makes the disease a public health concern in Iran. The objectives of the current study were to investigate the epidemiologic aspects of the animal bite and determine the associated risk factors of the delay in initiation of post-exposure prophylaxis (PEP) against rabies in Iran. Study Design: National registry-based cross-sectional study. Methods: This study included all registered cases of animal bites between March 2021 and March 2022 at the Ministry of Health and Medical Education in Iran. We retrieved epidemiologic data on person, time, place, and PEP outcome. Results: A total of 260470 animal bite cases (approximately 334 per 100000 populations, and 11 deaths) were registered during the study period. About 77.2% of them were reported in males, 4.3% in children aged less than 5 years, 56.4% occurred in urban areas, 98% in domestic animals, and mostly in north and northeast areas of Iran. Additionally, 2.8% of cases had a delay of more than 48 hours in the initiation of PEP. Significant determinants of the increase in delay were female gender (OR=1.43, 95% CI: 1.36, 1.51, P<0.001), foreign nationality (OR=1.19, 95% CI: 1.01, 1.12, P=0.001), rural residence (OR=1.07, 95% CI: 1.01, 1.12, P=0.010), and the wild animals (OR=1.22, 95% CI: 1.12, 1.34, P<0.001). Conclusion: The observed frequency of animal bites in a year indicates a serious public health concern and the need for targeted interventions, especially in at-risk areas and vulnerable populations.