Background: Clinical and experimental evidence regarding the influence of heart rate (HR) on arterial stiffness and its surrogate marker carotid-to-femoral pulse wave velocity (cf-PWV) is conflicting. We aimed to evaluate the effect of HR on cf-PWV measurement under controlled haemodynamic conditions and especially with respect to blood pressure (BP) that is a strong determinant of arterial stiffness. Method: Fifty-nine simulated cases were created using a previously validated in-silico model. For each case, cf-PWV was measured at five HR values, 60, 70, 80, 90, 100 bpm. With increasing HR, we assessed cf-PWV under two scenarios: with BP free to vary in response to HR increase, and with aortic DBP (aoDBP) fixed to its baseline value at 60 bpm, by modifying total peripheral resistance accordingly. Further, we quantified the importance of arterial compliance (C) on cf-PWV changes caused by increasing HR. Results: When BP was left free to vary with HR, a significant HR-effect on cf-PWV (0.66 +/- 0.24 m/s per 10 bpm, P < 0.001) was observed. This effect was reduced to 0.21 +/- 0.14 m/s per 10 bpm (P = 0.048) when aoDBP was maintained fixed with increasing HR. The HR-effect on the BP-corrected cf-PWV was higher in the case of low C = 0.8 +/- 0.3 ml/mmHg (0.26 +/- 0.15 m/s per 10 bpm, P = 0.014) than the case of higher C = 1.7 +/- 0.5 ml/mmHg (0.16 +/- 0.07 m/s per 10 bpm, P = 0.045). Conclusion: Our findings demonstrated that relatively small HR changes may only slightly affect the cf-PWV. Nevertheless, in cases wherein HR might vary at a greater extent, a more clinically significant impact on cf-PWV should be considered.