Abstract Purpose Predicting malignant progression of grade II gliomas would allow for earlier initiation of treatment. The hypothesis for this single-centre, case–control study was that the perfusion signal on ASL-MRI predicts such malignant progression in the following 12 months. Methods Consecutive patients with the following criteria were included: ≥ 18 years, grade II glioma (biopsied or resected) and an ASL-MRI 6–12 months prior to malignant progression (cases) or stable disease (controls). Malignant progression was defined either radiologically (new T1w-contrast enhancement) or histologically (neurosurgical tissue sampling). Three controls were matched with each case. Some patients served as their own control by using earlier imaging. The ASL-MRIs were reviewed by two neuroradiologists and classified as positive (hyper-intense or iso-intense compared to cortical grey matter) or negative (hypo-intense). In patients with epilepsy, a neurologist reviewed clinicoradiological data to exclude peri-ictal pseudoprogression. The statistical analysis included diagnostic test properties, a Cohen’s Kappa interrater reliability coefficient and stratification for previous radiotherapy. Results Eleven cases (median age = 48, IQR = 43–50 years) and 33 controls (43, 27–50 years) were included. Malignant progression appeared at 37 months (median, IQR = 17–44) after first surgery. Thirty ASL-MRIs were assessed as negative and 14 as positive. None of the MRIs showed signs of peri-ictal pseudoprogression. ASL significantly predicted subsequent malignant progression (sensitivity = 73%; specificity = 82%; OR = 12; 95%-CI = 2.4–59.1; p = 0.002). The interrater reliability coefficient was 0.65. In stratified analysis, ASL-MRI predicted malignant progression both in patients with previous radiotherapy and in those without (Mantel–Haenszel test, p = 0.003). Conclusion Perfusion imaging with ASL-MRI can predict malignant progression within 12 months in patients with grade II glioma.