Background: Information regarding clinical characteristics and response to treatments of IDH-wild type grade II gliomas are still lacking. This national retrospective study aimed to investigate natural history, management, factors affecting response to treatments and outcome of a cohort of WHO grade II IDH-wild type glioma patients. Methods: We collected all clinical data of patients diagnosed with WHO grade II IDH-wild type glioma from 1999 to 2017 in six major Italian Institutions. IDH mutation was assessed by either immunohistochemistry or sequencing (in cases with negative immunohistochemistry). Exclusion criteria were the presence of minimal anaplastic foci or radiological features of HGGs. Kaplan-Meier curves and Cox-regression models were used for univariate and multivariate analysis. Results: Overall, 194 patients were collected and ultimately 122 met the inclusion criteria. Median age was 45 years. Non-enhancing tumors on MRI accounted for 74% while 26% had minimal/mild contrast enhancement. Surgery consisted in gross total resection in 29%, partial/subtotal in 45%, biopsy in 24%, and unknown in 2%. According to WHO 2007 astrocytomas were 44%, oligodendrogliomas 35%, and mixed gliomas 21%. MGMT methylation was available in 68% of patients and in 40% of them was methylated. Post-surgical management consisted in watch and wait in 42%, chemoradiation in 21%, chemotherapy alone in 21%, radiotherapy alone in 5%, radiotherapy followed by chemotherapy in 5%, and 6% unknown. Median time of follow-up was 31 months. Progressive disease was observed in 64% of patients. Median PFS was 24.0 months (1.2 – 147.0), and median OS was 45.3 months (1.0 – 225.6). Factors positively associated with PFS and OS in univariate analysis were younger age, absence of contrast enhancement, and gross total resection. Age and extent of surgery retained a statistically significant importance in multivariate analysis. Conclusions: WHO grade II IDH-wild type gliomas have worse outcome compared with IDH-mutant tumors. This is the first study that details clinical and radiological presentation of this rare subgroup of tumors and suggests that gross total resection is critical in improving survival.