Abstract Introduction Noninvasively Doppler estimated coronary velocity (as a surrogate of flow) reserve (CVR) by adenosine is a useful parameter for risk stratification in chronic coronary syndromes (CAD). However, baseline velocity fluctuation due to sympathetic drive, as in mental stress, may affect the evaluation of the actual CVR. Aim Aim of the study was to assess the effect of b blocker administration following adenosine infusion in the coronary velocity and thus the consequences in the estimated CVR. Patients and methods Sixty (females 8) patients (pts) with stable CAD (mean/SD: age 64/10, ejection fraction % 55/8) were studied before the performance of a dobutamine stress echo. Distal left anterior descending (LAD) velocity was estimated at rest (CVrest), at maximal adenosine infusion (140γ/kg/min: CVaden) and following esmolol infusion 3–5 min later (CVbbl). CVR was estimated using as baseline velocity either CVrest (CVRrest) or CVbbl (CVRbbl). Respective changes of heart rate (HR) and systolic blood pressure (SBP) were also estimated. Results CVbbl was smaller than CVrest (23/7 vs 29/13, p<0.0.01). Thus, CVRbbl was greater than CVRrest (3/0.9 vs 2.7/0.6, p<0.001) with an absolute difference (dCVR) of 0.46/0.84, a % difference (%dCVR) of 23/34%, with a modest linear relationship (R2=0.08, p=0.02 figure). The %dCVR was also linearly related to CVRrest (R2=0.13, p=0.003 figure) and it was independent from age, HR/BP changes and the dobutamine stress echo outcome. Differences between CVRbbl and CVRrest were greater in females (females/males: dCVR 1.2/0.9 vs 0.36/0.8, %dCVR 0.67/0.56 vs 0.36/0.26, both p<0.001). Conclusions Noninvasively estimated CVR is affected by the baseline sympathetic tone, irrespectively from the age in stable CAD. A gender effect is evident, reiterating the microvascular susceptibility in females. Thus, potential mental stress background must be considered, and b-blockade subsequently might be applied during CVR evaluation to overcome any sympathetic effect. Funding Acknowledgement Type of funding sources: None.