Introduction: The role of perfusion neuroimaging in managing cases of acute ischemic stroke (AIS) is to identify ischemic penumbra and regions of hypo-perfusion, which can be salvaged. Dynamic susceptibility contrast (DSC) perfusion imaging techniques have been the main magnetic resonance imaging (MRI) perfusion techniques used to identify AIS. Arterial spin labelling (ASL) is an alternative non-invasive perfusion technique, which permits tissue perfusion measurement without any need for administration of exogenous contrast agents. The objective was to compare the diagnostic accuracy of ASL perfusion MRI versus DSC enhanced perfusion MRI in detecting perfusion-diffusion mismatch of varying volumes in acute ischemic stroke.Materials and methods: A hospital-based observational cross-sectional study was done in a tertiary care institute in Tamil Nadu between December 2018 to October 2019. Fifty-five subjects aged more than 18 years referred to the Radio-diagnosis department (less than 24 hours since the onset of weakness) for emergency assessment of suspected acute stroke were subjected to MRI stroke scan protocol. Then AIS cases were evaluated with ASL and DSC perfusion-weighted imaging. The collected data was entered in Excel (Microsoft, Redmond, WA, USA). IBM SPSS version 22 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. Receiver operating characteristic (ROC) analysis was done to assess the predictive validity of ASL in predicting DSC mismatch. The diagnostic accuracy of ASL was the primary outcome variable. P-value < 0.05 was considered statistically significant.Results: Forty-four subjects confirmed as stroke were included in the final analysis. Their mean (±SD) age was 53.84 (±10.80) years. 72.7% were males. The majority (53.8%) presented during the acute stage of cerebral infarction (53.8%). The majority (45.5%) had hemiplegia followed by aphasia (27.3%). The major vascular territory involved was the middle cerebral artery (54.5%). The sensitivity, specificity, positive predictive value, and negative predictive value of ASL (non-contrast) in predicting DSC (contrast) mismatch was found to be 71.43%, 78.57%, 83.33%, and 64.71% respectively.Conclusion: ASL MR has the potential to replace MRI DSC perfusion in the future imaging diagnostic work-up for stroke. However, further studies are required to validate its role as the first-line imaging for stroke therapy.