Thrombocytopenia is one of the side effects of VPA. This study aimed to evaluate the incidence and risk factors of thrombocytopenia after intravenous VPA treatment in children with neurosurgical operations. Pediatric patients undergoing neurosurgical operations treated with intravenous VPA were enrolled in this retrospective study. According to platelet count after intravenous injection of VPA, the pediatric patients were divided into the thrombocytopenia group and the non-thrombocytopenia group. Binary logistic regression analysis was used to explore the risk factors for thrombocytopenia. A total of 252 children with neurosurgical operations were included in this study, and the incidence of thrombocytopenia was 12.3% (31/252). Univariate analysis showed that baseline platelet count, duration of VPA therapy, and blood loss were associated with the occurrence of thrombocytopenia after intravenous administration of VPA. Binary logistic regression revealed that baseline platelet count (OR 0.995, 95% CI 0.991-0.999) and blood loss (OR 0.995, 95% CI 0.991-0.999) were independent risk factors for thrombocytopenia after intravenous VPA in children undergoing neurosurgical operations. Our data show that thrombocytopenia is common in neurosurgical operations children treated with intravenous VPA, and that baseline platelet count is an independent risk factor for thrombocytopenia. Regular monitoring of baseline platelet count is important for whether to short-term prophylactic use intravenous VPA in children undergoing neurosurgical operations.