Abstract: Objective To enhance the awareness of diagnose and treatment of venous thrombus in premature infants. Methods The clinical features, treatment and prognosis of lower limb vein thrombus in three case of premature infants were retrospectively analyzed. Results Three premature infants of gestational age 29-36 weeks were found thrombosis in 1-57 days after birth. One case received peripherally inserted central cathete (PICC). All of three cases had infection signs and trauma. One case received thrombolytic and anticoagulant therapy, one case received high dose thrombolytic therapy, and both of them were treated successfully without bleeding complication. However, another case was deteriorated after giving up treatment. Conclusions Critically ill premature infants are at high risk of thrombosis. Infection, indwelling tube, thrombophilia constitution, and maternal risk factors were the high risk factors of thrombosis. Early detection, early diagnosis, and effective individualized treatment can improve the prognosis.