Background: The influence of age-dependent changes on fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) and the response to pharmacological hyperaemia has not been investigated. Aims: We investigated the impact of age on these indices. Methods: This is a post hoc analysis of the ADVISE II trial, including a total of 690 pressure recordings (in 591 patients). Age-dependent correlations with FFR and iFR were calculated and adjusted for stenosis severity. Patients were stratified into three age terciles. The hyperaemic response to adenosine, calculated as the difference between resting and hyperaemic pressure ratios, and the prevalence of FFR-iFR discordance were assessed. Results: Age correlated positively with FFR (r=0.08, 95% CI: 0.01 to 0.15, p=0.015), but not with iFR (r=-0.03, 95% CI: -0.11 to 0.04, p=0.411). The hyperaemic response to adenosine decreased with patient age (0.12±0.07, 0.11±0.06, 0.09±0.05, for the 1st [33-58 years], 2nd [59-69 years] and 3rd [70-94 years] age tertiles, respectively, p<0.001) and showed significant correlation with age (r=-0.14, 95% CI: -0.21 to -0.06, p<0.001). The proportion of patients with FFR ≤0.80+iFR >0.89 discordance doubled in the first age tercile (14.1% vs 7.1% vs 7.0%, p=0.005). Conclusions: The hyperaemic response of the microcirculation to adenosine administration is age dependent. FFR values increase with patient age, while iFR values remain constant across the age spectrum. These findings contribute to explaining differences observed in functional stenosis classification with hyperaemic and non-hyperaemic coronary indices.