OBJECTIVE: To analyze the sclerotherapy of giant (≥8 mm) lymphatic malformations in neonates and discuss effective treatment. METHODS: This was a single-center retrospective study. Twelve patients received bleomycin (BLM) (six patients) or BLM combined with polidocanol (POL) (eight patients). The safety and effects of BLM and BLM + POL were analyzed using a t-test for categorical data and likelihood ratios or Fisher's exact test for continuous data. Factors resulting in an increased number of treatment sessions were studied. RESULTS: Treatment began 2-5 days after birth. The patients in the BLM group underwent more treatment sessions. Gestational age, lesion size and type, total response, and complications showed no significant differences between groups. Larger and mixed-ype lesions required more treatment sessions. CONCLUSIONS: Both BLM group and BLM + POL group appear relatively safe and effective in neonates with giant lymphatic malformations. The combination of the two agents reduced the number of procedures and general anesthesia required.