In critically ill infants, there exists a susceptibility to develop thrombosis due to several risk factors. Knowing thrombosis-related risk factors would be beneficial in developing a risk prediction model to avert thrombosis and in improving results. Findings of this study contribute to the understanding of the differences in risk factors for venous vs arterial thrombosis in neonates and to the knowledge of the links of central access device (CAD) features with neonatal thrombosis.

• In this case-control study, 118,952 new admissions to 31 neonatal intensive care units (NICUs) were analyzed to determine risk factors related to venous and arterial thrombosis in neonates admitted to the NICU and to determine differences in risk factors for venous vs arterial thrombosis.

• For thrombosis, the overall incidence was estimated to be 15·5 per 1,000 NICU admissions (95% CI 14·8–16·2).

• Venous thrombosis was found to be independently linked with bloodstream infection (odds ratio 2·07), maternal diabetes (1·62), abdominal or gastrointestinal surgery (1·36), thrombocytopenia (2·44), prolonged mechanical ventilation (1·27), and age 7 days or older at admission (1·49).

• An independent association of arterial thrombosis with the following factors was found: maternal hypertension (1·42), thrombocytopenia (2·20), prolonged mechanical ventilation (1·58), age 7 days or older at admission (1·35), and small for gestational age (1·56).

• In the CAD subset analysis, higher odds of thrombosis were noted in relation to CAD duration of 21 days or longer and CAD in both the upper and lower body.