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Background In stable coronary artery disease (CAD), the primary goal of percutaneous coronary intervention (PCI) is symptom relief. Fractional flow reserve (FFR) and non-hyperaemic pressure ratios such as resting full-cycle ratio (RFR) are used to guide revascularisation. While these indices correlate with myocardial ischaemia, they have never been validated against the onset of angina. The physiological thresholds for angina (FFR angina and RFRangina) at rest and during exercise remains undefined.Methods This was a multicentre, double-blind, randomised, placebo-controlled study in patients with stable angina and single-vessel CAD. Following imaging-guided PCI, an in-stent balloon was incrementally inflated until angina occurred at rest. This angina threshold was verified against placebo inflation, and corresponding FFR angina and RFRangina values were measured at symptom onset. The protocol was repeated during low- and high-intensity exercise to assess change in angina thresholds with increasing cardiac workload.Results Sixty-five patients were enrolled (mean age 63.9 ± 8.7 years; 74% male; 90.8% had Canadian Cardiovascular Society class II or III angina). Median pre-PCI FFR and RFR were 0.59 (IQR 0.46–0.70) and 0.61 (IQR 0.40–0.82), respectively, improving post-PCI to 0.88 (IQR 0.84–0.92) and 0.92 (IQR 0.90–0.94). During the research protocol, median FFR angina at rest was 0.29 (IQR 0.23–0.35), increasing to 0.38 (IQR 0.30–0.48) during low-intensity exercise and 0.45 (IQR 0.36–0.55) during high-intensity exercise. RFRangina similarly increased from 0.22 (IQR 0.16–0.30) at rest to 0.26 (0.18-0.36) and 0.32 (0.23-0.46) with low- and high-intensity exercise. All thresholds were significantly lower than clinical diagnostic cutpoints (P<0.001). Lower FFRangina and RFRangina thresholds were associated with greater symptom reproducibility across resting, low-and high-intensity exercise conditions (FFRangina: P=0.008, <0.001, <0.001, respectively; RFRangina: P=0.015, <0.001, 0.002, respectively). Lower angina thresholds across these conditions predicted both, higher baseline angina burden and greater angina relief with PCI (Pr(interaction)>0.999).Conclusion Physiological thresholds for angina (FFR angina and RFRangina) were highly individualised, workload-dependent, and substantially lower than ischaemia-based clinical cutpoints. A personalised, symptom-guided strategy is essential to improve patient selection and achieve meaningful angina relief with PCI.