Abstract BACKGROUND Postoperative posterior fossa syndrome (PFS) has historically been diagnosed as present vs. absent despite a continuum of severity in presentations. We recently demonstrated categorizing children into PFS1 (complete mutism) and PFS2 (diminished speech) has prognostic utility for neurological recovery. Given children who experience PFS are also at increased risk for neurocognitive impairments, we investigated whether these PFS variants predict neurocognitive outcomes while considering well-established risk factors (i.e., age and treatment intensity). METHODS Children treated for medulloblastoma at St. Jude on a prospective, risk-stratified protocol (SJMB12; NCT 01878617) were study eligible if they had at least two neurocognitive evaluations. SJMB12 participants received neurological and neurocognitive evaluations prior to irradiation and annually for 5 years. Neurocognitive outcomes included intellectual functioning (Wechsler Intelligence Scale for Children [WISC-IV] estimated IQ [EIQ]), processing speed (WISC-IV Processing Speed Index [PSI]), working memory (WISC-IV Working Memory Index [WMI]), and adaptive functioning (Behavior Assessment System for Children [BASC2] Activities of Daily Living [ADL]). RESULTS 149 patients (age at diagnosis= 10.7±5.6; 64% male; 9% 15Gy, 40% 23.4Gy, 51% ≥36Gy) were included. No significant differences between PFS1 (n=34) or PFS2 (n=16) compared to NonPFS (n=99) were identified in age, sex, or irradiation dose (ps>.05). Multivariable linear mixed models indicate NonPFS have better EIQ than PFS1 and PFS2 (p<.03), with EIQ improving over time (p=.01). NonPFS have better PSI than PFS1 and PFS2 (p<.001). PSI declines over time irrespective of age (p>.05); however, PSI declines for those receiving 36Gy while improving for those receiving 15Gy (p<.001). NonPFS have better WMI than PFS1 and PFS2 (p<.05); older age at diagnosis is associated with improvement in WMI over time (p<.0005). ADL declines only in PFS1 patients (p<.05). CONCLUSIONS PFS variants add value beyond established risk factors in predicting neurocognition. Severity of PFS, in addition to treatment intensity, predicts worse outcomes.