Objective To investigate the risk factors associated with recurrence of high-grade non-functioning pituitary neuroendocrine tumors(NF-PitNETs)following total resection.Methods A retrospective study was conducted on the clinical data of 252 patients with high-grade NF-PitNETs who underwent surgical treatment at the Department of Neurosurgery,Beijing Tiantan Hospital from January 2012 to December 2023,and met the inclusion criteria.High-grade NF-PitNETs included Knosp 3A,3B,and 4-grade subtypes.Kaplan-Meier curves and Log-rank tests were employed to compare the progression-free survival(PFS)of Knosp 3A,3B,and 4-grade patients.Cox regression analysis was applied to identify the risk factors associated with the recurrence of high-grade NF-PitNETs.Receiver operating characteristic(ROC)curve was used to calculate the area under the curve(AUC)of each recurrence-related factor to evaluate the diagnostic efficiency.Results Survival analysis revealed that there were significant differences in PFS among Knosp 3A,3B,and 4-grade patients(P<0.001).The PFS of Knosp 3A was significantly better than that of grade 3B and 4-grade(P<0.05),while there was no significant difference between Knosp 3B and 4-grade(P=0.118).After integrating the three groups into Knosp 3A group and 3B-4 group,there were significant differences in PFS and some clinical features between the two groups(P<0.05).Cox regression analysis indicated that age<55 years old(HR=2.883,95%CI 1.253-6.634;P=0.013),T2 heterogeneous signal(HR=1.842,95%CI 1.061-3.197;P=0.030),Knosp 3B-4(HR=2.190,95%CI 1.069-4.488;P=0.032),and Ki-67≥3%(HR=2.266,95%CI 1.265-4.061;P=0.006)were risk factors related to tumor recurrence.ROC curve analysis showed that the AUCs of the above-mentioned risk factors were 0.682,0.706,0.709 and 0.750,respectively,and the AUC of the multi-factor combined model(age+T2 signal+Knosp grade+Ki-67)was 0.838,which was significantly larger than that of each single risk factor(P<0.05).Conclusion High-grade NF-PitNETs patients with age<55 years old,T2 heterogeneous signal,Knosp 3B-4 and Ki-67≥3%have a higher recurrence risk.The combined application of multiple risk factors can improve the predictive value of recurrence.