As crucial factors in blood clot formation, shear stress distribution and low flow zones are assessed in different central venous catheter tip designs by using a combined numeric and experimental approach. Computational Fluid Dynamics was validated with Particle Image Velocimetry by comparing simulated and measured velocities and shear strains in three designs of the blood withdrawing arterial lumen: cylindrical and with tip (1) cut straight, (2) cut at an angle, or (3) cut straight with a sleeve entrance. After validation, four additional designs were studied: (4) with two side holes and tip cut straight or (5) at an angle, (6) concentric lumens, and (7) Ash Split-based. In these seven designs, shear stress (SS), blood residence time (RT), and Platelet Lysis Index, which combines the influence of shear stress magnitude and exposure time, were simulated. Concentric catheter was discarded due to highly elevated SS. Ash Split-based design had elevated RT values in the distal tip zone as major inflow occurs through the most proximal side holes, but this is compensated by low average SS. A straight-cut tip and possibly two side holes are preferred when aiming at minimal SS and RT. These data may lead to more patent catheters.