Background: Femoral dP/dt (maximum rate of the arterial pressure increase during systole) measured by pulse contour analysis has been proposed as a surrogate of left ventricular (LV) dP/dt and as an estimator of LV systolic function. However, femoral dP/dt may be influenced by LV loading conditions. In this study, we evaluated the impact of variations of LV systolic function, preload and afterload on femoral dP/dt in critically ill patients with cardiovascular failure to ascertain its reliability as a marker of LV systolic function. Results: We performed a prospective observational study to evaluate changes in femoral dP/dt, thermodilution-derived variables (PiCCO2-Pulsion Medical Systems, Feldkirchen, Germany) and LV ejection fraction (LVEF) measured by transthoracic echocardiography during variations in dobutamine and norepinephrine doses and during volume expansion (VE) and passive leg raising (PLR). Correlations with arterial pulse and systolic pressure, effective arterial elastance, total arterial compliance and LVEF were also evaluated. In absolute values, femoral dP/dt deviated from baseline by 21% (201 ± 297 mmHg/s; p = 0.013) following variations in dobutamine dose (n = 17) and by 15% (177 ± 135 mmHg/s; p < 0.001) following norepinephrine dose changes (n = 29). Femoral dP/dt remained unchanged after VE and PLR (n = 24). Changes in femoral dP/dt were strongly correlated with changes in pulse pressure and systolic arterial pressure during dobutamine dose changes (R = 0.942 and 0.897, respectively), norepinephrine changes (R = 0.977 and 0.941, respectively) and VE or PLR (R = 0.924 and 0.897, respectively) (p < 0.05 in all cases). Changes in femoral dP/dt were correlated with changes in LVEF (R = 0.527) during dobutamine dose variations but also with effective arterial elastance and total arterial compliance in the norepinephrine group (R = 0.638 and R = − 0.689) (p < 0.05 in all cases). Conclusions: Pulse contour analysis-derived femoral dP/dt was not only influenced by LV systolic function but also and prominently by LV afterload and arterial waveform characteristics in patients with acute cardiovascular failure. These results suggest that femoral dP/dt calculated by pulse contour analysis is an unreliable estimate of LV systolic function during changes in LV afterload and arterial load by norepinephrine and directly linked to arterial waveform determinants.