Purpose: To evaluate vascular function and its relationship to cardiorespiratory fitness in professional handball athletes. Method: We examined 30 male professional handball athletes (age 27 [plus or minus] 4 y) and 10 male sedentary controls (age 26[plus or minus] 5 y) at rest. The workup included exercise testing via ergometry. To assess vascular function, a validated electronic model of the arterial tree (vasc assist 2 [Registered Trade Mark]) was used. It replicates noninvasively acquired pulse pressure waves by modulating the relevant functional parameters of compliance, resistance, inertia, pressure, and flow. The maximum oxygen uptake (VO2max) was estimated using the validated heart rate ratio method. Results: Athletes had a significantly lower systolic and diastolic central blood pressure ([mini c]BP) compared to controls (102[plus or minus]9/60[plus or minus] 9 vs. 110[plus or minus]8/74[plus or minus]9 mmHg, p[less than] 0.01), whereas aortic pulse wave velocity (PWV) (6.2[plus or minus]0.8 vs. 6.3[plus or minus] 0.5 m/s, p = 0.45) and augmentation index at a heart rate of 75 (Aix[at]75) (-4[plus or minus]12 vs. -13[plus or minus]16%, p = 0.06) were not different. Resistance index (R) (15.9[plus or minus]4.4 vs. 10.6[plus or minus]0.6, p = 0.001) and maximum power output (MPO) (3.55 [plus or minus]0.54 vs. 2.46[plus or minus]0.55 Watt/kg, p[less than] 0.001) were significantly higher in athletes compared to controls. We found no relevant correlation between MPO, resting heart rate, PWV, Aix[at]75, and cBP. A higher VO2max (p = 0.02) and a lower R (p[less than]0.01) were significant predictors of a higher MPO in athletes. Conclusion: R had an independent and strong correlation to MPO in athletes, which might help to disentangle the contribution of aerobic capacity and arterial function to physical power.