Abstract Background Coronary pressure- and flow-derived parameters that reflect resting and hyperemic conditions have prognostic value, but their relative prognostic implications has not been established. Purpose To evaluate the individual and combined prognostic relevance of hyperemic pressure, hyperemic flow, resting pressure, and resting flow Methods A total of 1,971 vessels, in which revascularization was deferred after invasive pressure and flow assessment, were included from the international, multicenter registry composed of 16 hospitals across 7 countries. Abnormal resting pressure and flow were defined as a distal coronary pressure/aortic pressure (Pd/Pa) ≤0.92 and high resting flow (1/resting mean transit time [Tmn] >2.4 or resting average peak flow [APV]>22.7 cm/s), and abnormal hyperemic pressure and flow, as fractional flow reserve (FFR) ≤0.80 and low hyperemic flow (1/hyperemic Tmn <2.2 or hyperemic APV <25.0 cm/s), respectively. The clinical endpoint was target vessel failure (TVF), target vessel-myocardial infarction (MI), or cardiac death at 5 years. Results The mean age of patients was 62.8 ± 10.2 years, and the mean % diameter stenosis was 46.8±16.5%. Abnormal pressure and flow were independent predictors of TVF (HR 1.83 [95% CI, 1.25–2.68], P =0.002 for high resting flow; HR 2.89 [2.04–4.10], P <0.001 for low resting Pd/Pa; HR 1.87 [1.16–3.00], P =0.010 for low hyperemic flow; HR 3.13 [2.22–4.41], P <0.001 for low FFR) and cardiac death/MI (HR 1.99 [1.16–3.42], P =0.013 for high resting flow; HR 3.28 [1.99–5.39], P <0.001 for low resting Pd/Pa; HR 2.20 [1.12–4.32], P =0.022 for low hyperemic flow; HR 3.11 [1.91–5.07], P <0.001 for low FFR). In the order of neither, either, and both abnormal resting pressure and flow, the risk of 5-year TVF or cardiac death/MI increased proportionally (P-for-trend <0.001). This was also true for abnormal hyperemic pressure and flow (P-for-trend <0.001). In 1,640 vessels with normal FFR, a higher clinical event rate was observed when the vessels had a high resting flow (HR 2.08 [1.28–3.37], P =0.003 for TVF; HR 2.11 [1.04–4.27], P =0.039 for cardiac death/MI) or low resting Pd/Pa (HR 3.14 [1.90 – 5.19], P <0.001 for TVF; HR 3.49 [1.70–7.18], P <0.001 for cardiac death/MI). Similarly in 1,556 vessels with a normal resting Pd/Pa, a higher event rate was related to a low hyperemic flow (HR 2.13 [1.17–3.84], P =0.014 for TVF; HR 2.73 [1.16–6.33], P =0.021 for cardiac death/MI) or low FFR (HR 3.86 [2.35–6.34], P <0.001 for TVF; HR 3.50 [1.71–7.19], P <0.001 for cardiac death/MI) (Figure). Overall results were similar when the different cut-off values for pressure and flow parameters were applied. Conclusions Abnormal resting and hyperemic pressure and flow were independent prognostic predictors. The abnormal flow had an additive prognostic value for pressure in both resting and hyperemic conditions. Resting and hyperemic parameters showed complementary prognostic implications.