Abstract BACKGROUND Diffuse intrinsic pontine glioma (DIPG) is one of the most aggressive pediatric central nervous system tumors, and currently, there are no curative treatment options available. With the increasing application of molecular diagnostics, more and more DIPG patients are recommended to undergo surgery; however, its correlation with dissemination needs to be better understood. Hence, we conducted this cohort to analyze the predictors of subsequent metastasis in pediatric DIPGs. METHODS The final analysis included 142 pediatric (age ≤ 12) DIPG patients treated at Sanjiu Brain Hospital between January 2017 and September 2023. The data were retrospectively collected following the initial diagnosis. Patients were followed up for 6 months. The primary endpoint was the occurrence of subsequent metastasis. Univariable and multivariable logistic regression analyses were utilized to identify statistically significant predictors of subsequent dissemination. All statistical assessments were two-tailed, and only P < 0.05 was deemed to be statistically significant. RESULTS Among 142 patients, 14(9.9%) developed metastasis within the follow-up time. There were 77(54.2%) males and 65(45.8%) females. The median age was 7 years (ranging 1 - 12 years). The overall cohort demonstrated that surgery was the only predictor of dissemination both in univariable (OR 4.567, 95%CI 1.351 – 20.901, P = 0.024) and multivariable (OR 5.501, 95%CI 1.560 – 26.105, P = 0.014) analyses. However, subgroup analysis involving patients who received surgical intervention showed that biopsy was not superior nor inferior to resection in terms of relative risk for subsequent dissemination (16.7% vs. 15.8%). CONCLUSION Surgical intervention increases the relative risk of dissemination occurrence to four times more than those who did not receive surgery. Surgical intervention is crucial given the potential of molecular analysis leading to improved therapeutic options. Nonetheless, patients should be informed about the risks associated with surgery, including subsequent metastasis.