Background: Despite increasing clinical use, there is limited data regarding regadenoson in stress perfusion cardiovascular magnetic resonance (CMR). In particular, given its long half-life the optimal stress protocol remains unclear. Although Myocardial Perfusion Reserve (MPR) may provide additive prognostic information, current techniques for its measurement are cumbersome and challenging for routine clinical practice.The aims of this study were: 1) To determine the feasibility of MPR quantification during regadenoson stress CMR by measurement of Coronary Sinus (CS) flow; and 2) to investigate the role of aminophylline reversal during regadenoson stress-CMR., Methods: 117 consecutive patients with possible myocardial ischemia were prospectively enrolled. Perfusion imaging was performed at 1 minute and 15 minutes after administration of 0.4 mg regadenoson. A subgroup of 41 patients was given aminophylline (100 mg) after stress images were acquired. CS flow was measured using phase-contrast imaging at baseline (pre CS flow), and immediately after the stress (peak CS flow) and rest (post CS flow) perfusion images., Results: CS flow measurements were obtained in 92% of patients with no adverse events. MPR was significantly underestimated when calculated as peak CS flow/post CS flow as compared to peak CS flow/pre CS flow (2.43±0.20 vs. 3.28±0.32, p=0.03). This difference was abolished when aminophylline was administered (3.35±0.44 vs. 3.30±0.52, p=0.95). Impaired MPR (peak CS flow/pre CS flow<2) was associated with advanced age, diabetes, current smoking and higher Framingham risk score., Conclusions: Regadenoson stress CMR with MPR measurement from CS flow can be successfully performed in most patients. This measurement of MPR appears practical to perform in the clinical setting. Residual hyperemia is still present even 15 minutes after regadenoson administration, at the time of resting-perfusion acquisition, and is completely reversed by aminophylline. Our findings suggest routine aminophylline administration may be required when performing stress CMR with regadenoson.