Background: Regadenoson is a selective A2A receptor agonist that is used for vasodilator stress myocardial perfusion imaging (MPI). Since the drug is partially metabolized by the liver, its safety in patients with end-stage liver disease (ESLD) needs to be determined. Methods and Results: We studied 168 consecutive patients with ESLD who had regadenoson stress gated single photon emission computed tomography MPI between January 2008 and March 2010 before planned orthotopic liver transplantation and compared the hemodynamic responses and safety profile to 168 control patients. There were 72 women (43%) in ESLD versus 87 (52%) in the control group (P = .1). The patients with ESLD were younger (58 ± 7 vs 62 ± 12 years, P = .0002), but more likely to be Caucasians (P = .002). The MPI images were normal in 161 patients (96%) in each group. The left ventricular ejection fraction was 72 ± 10% in ESLD and 66 ± 11% in the control patients (P = .0001). The heart rate increase in response to regadenoson was lower in patients with ESLD than in the control group (16 ± 11 vs 23 ± 16 bpm, P = .0001), but the changes in systolic and diastolic blood pressures were similar (-9 ± 12 vs -11 ± 14 mmHg and -6 ± 8 vs -7 ± 10 mmHg, respectively, P = NS). There were no deaths or medication-related adverse events that required hospitalization in either group within 30 days of the study. Conclusion: This is the first study to document the tolerability and safety profile of regadenoson in patients with ESLD. © 2010 American Society of Nuclear Cardiology.