Background: Neonatal thrombosis is a rare disorder usually develops because of underlying conditions in the neonatal period, such as thrombophilia gene mutations, sepsis, congenital heart disease and surgical interventions or intravascular catheters. Objective: The goal is to look at the prevalence of neonatal thrombophilia and its risk factors among neonates admitted to the Neonatal Intensive Care Unit (NICU). Submit Date Revise Date Accept Date 2022-06-13 2022-07-15 2022-07-22 Patients and methods: A cohort research that took place in neonatal ICUs in Zagazig University Hospitals from January to December 2021. Forty patients were involved. Patients were given a thorough medical history, clinical, neurological examinations, laboratory routine tests and Screening for thrombophilia gene variants by RT-PCR using the Vienna Lab Diagnostics GmbH's (FVL, PTH and MTHFR Strip Assay) ® A kit (Vienna, Austria). Results: Concerning factor V gene mutation (G1691A) there was 6 (15%) had mutations, four of them (10%) showed heterozygous and two (5%) showed homozygous s mutations while 34 (85%) were normal. Nine (22.5%) patients had mutation of prothrombin G2010A gene with five (12.5%) of them were heterozygous and four (10%) were homozygous while 31 (77.5%) were normal. As regard MTHR C677T, 10 (25%) were normal, 23 (57.5%) had heterogeneous and 7 (17.5%) showed homozygous mutations. There was statistically significant increase in D-dimer and the presence of the Factor V (G1691A) and prothrombin G20210A while it was non-significant as regard mutations of MTHFR C677T. Conclusion: Neonatal thrombosis is a critical condition. Its incidence increased with the presence of homozygous thrombophilia gene mutations especially with surgical intervention or venous catheterization.