BACKGROUND: Little is known about the similarity of microcirculation assessment outcomes performed with regadenoson and adenosine. The aim of the current study was to compare coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) assessment using adenosine and regadenoson, and to evaluate predictors regarding the size of differences. METHODS: 44 patients were enrolled and diagnosed between 2021 and 2023. Fractional flow reserve (FFR), CFR and IMR were measured twice in the circumflex (Cx) (n = 8) or left anterior descending (LAD) (n = 36) artery: once with continuous infusion of adenosine (Adenocor 140 µg/kg/min) and 10 minutes later with regadenoson (Rapiscan 400 µg i.v.). RESULTS: Averaged results were quantified with adenosine and regadenoson for FFR (0.81 [0.75 ÷ 0.89] vs. 0.80 [0.73 ÷ 0.88]), CFR (3.84 [1.67 ÷ 4.08] vs. 3.97 [1.78 ÷ 4.32]) and IMR (20.01 [11 ÷ 24.5] vs. 20.25 [10.75 ÷ 23]), respectively. None of the differences were statistically significant. Among the significant (p <
0.05) predictors of greater ΔCFR, the following can be noted: prior percutaneous transluminal angioplasty/carotid artery stenting (β = 2.35), oral anticoagulant usage (β = 0.89), and prior stroke/transient ischaemic attack (TIA) (β = 1.09), with the latter being also confirmed for greater ΔIMR (β = 8.89). Moreover, patients with New York Heart Association (NYHA) class II/III, as compared to those with NYHA class I, were more likely to have greater ΔIMR (β = 11.89). CONCLUSIONS: Regadenoson may be a feasible alternative to adenosine in coronary microcirculation assessment, as it produces similar outcomes. Selected factors were found to be predictors of greater differences in IMR, CFR and FFR values according to the agent used for coronary hyperemia.