Introduction: Venous access in neonates is a basic yet critical component in neonatal intensive care unit (NICU). Central venous access and peripheral intravenous access are mostly preferred for delivering medications and intravenous fluids. This study aimed to compare the risks involved in central venous catheters and peripheral intravenous lines among term neonates. Methods: A prospective cohort study was carried out among 78 term neonates in the NICU of a tertiary care center in puducherry in India. Convenience sampling technique was used to enroll the neonates who met the inclusion criteria. Data pertaining to demographic and clinical characteristics, cannulation details, indwelling time, and incidence of thrombosis, phlebitis, occlusion, extravasation, and sepsis were collected by direct observation and from case record. Data were analyzed using SPSS software version 21. To analyze the data, descriptive statistics including frequency, percentage, mean, and standard deviation and inferential statistics including Fisher’s exact test were utilized. Results: Our findings indicated that the risks of thrombosis and phlebitis were significantly higher in peripheral intravenous line group than the central venous group. There was no statistically significant association between the risks and demographic and clinical characteristics in both of the venous access system. Conclusion: According to our results, the use of central venous catheter among neonates showed lower risks than peripheral intravenous lines. Hence, using central venous catheter may be given priority in the NICUs.