Objectives: This study aimed to compare maternal and neonatal side effects of natural vaginal delivery (NVD) under neuro-axial analgesia with usual NVD and C-section. Methods: In this single center prospective cohort study, deliveries carried out in a 7 months' period were evaluated after getting informed consent. The study is approved by the ethics committee of Shahid Beheshti University of Medical Sciences. Mothers were categorized into 3 groups of C-section, NVD with an analgesia, intervention, and usual NVD. Afterwards, maternal and neonatal side effects after delivery were assessed using physical examinations, laboratory results, and interviews. Results: Overall, 121 mothers were equally assigned to 3 groups. No significant differences were found in the first and fifth-minute APGAR scores of the neonates born in these 3 groups. Moreover, none of the neonates' fifth-minute APGAR scores were less than 7. In addition, hypoxia (umbilical artery pH < 7.2) was observed more in the neonates delivered by NVDs with analgesia interventions compared to the other 2 groups. In comparison with the mothers in the other 2 groups, headache and pruritus were more prevalent among the mothers who had NVDs under neuro-axial analgesia. Conclusions: Given the advantages of natural vaginal deliveries for mothers and their fetuses and considering the side effects of C-sections without medical indications, propagating painless NVDs could be a proper solution for increasing the prevalence rate of NVDs in the society. Conducting further studies on larger samples is recommended.