BACKGROUND: Coronary microvascular dysfunction is a clinically significant component of ischemic heart disease. There can be heterogenous patterns of coronary microvascular dysfunction defined by invasive physiologic indexes such as coronary flow reserve (CFR) and index of microcirculatory resistance (IMR). We sought to compare the prognosis of coronary microvascular dysfunction according to different patterns of CFR and IMR. METHODS: The current study included 375 consecutive patients undergoing invasive physiologic assessment for suspected stable ischemic heart disease and intermediate but functionally nonsignificant epicardial stenosis (fractional flow reserve, >0.80). According to cutoff values of invasive physiologic indexes reflecting microcirculatory function (CFR, <2.5; IMR, ≥25), patients were classified into 4 groups: (1) preserved CFR and low IMR (group 1), (2) preserved CFR and elevated IMR (group 2), (3) depressed CFR and low IMR (group 3), and (4) depressed CFR and elevated IMR (group 4). Primary outcome was a composite of cardiovascular death or admission for heart failure during the follow-up time. RESULTS: Cumulative incidence of the primary outcome was significantly different among the 4 groups (group 1, 20.1%; group 2, 18.8%; group 3, 33.9%; and group 4, 45.0%; overall P <0.001). Depressed CFR had significantly higher risk of primary outcome than preserved CFR in both low (hazard ratio [HR], 1.894 [95% CI, 1.112–3.225]; P =0.019) and elevated IMR subgroups (HR, 3.307 [95% CI, 1.519–7.202]; P =0.003). Conversely, the risk of primary outcome was not significantly different between elevated and low IMR in preserved CFR subgroups (HR, 0.926 [95% CI, 0.428–2.005]; P =0.846). Furthermore, as continuous variables, IMR-adjusted CFR (adjusted HR, 0.644 [95% CI, 0.537–0.772]; P <0.001) was significantly associated with the risk of primary outcome but CFR-adjusted IMR (adjusted HR, 1.004 [95% CI, 0.992–1.016]; P =0.515) was not. CONCLUSIONS: Among patients with suspected stable ischemic heart disease who were found to have an intermediate but functionally nonsignificant epicardial stenosis, depressed CFR was associated with an increased risk of cardiovascular death and admission for heart failure. However, elevated IMR alone with preserved CFR showed limited prognostic value in this population.