Thrombus formation and resulting thromboembolism are major risks that can impede the widespread use of ventricular assist devices (VADs). Adverse flow patterns (turbulence and stasis) have been implicated in thrombogenesis. This study focuses on optimization of VAD geometry, port orientation, and fluid dynamics to reduce thrombus formation. Particle image velocimetry with cross-correlation was performed using Amberlite particles suspended in distilled water. The transparent VADs were illuminated by halogen lamps. Four different VADs were tested in an iterative approach toward optimization. A peak shear stress of 9,100 dynes/cm2 was noted in the first configuration immediately after the end of systole at the outlet port. Modifications in chamber geometry, port diameters and orientation, and valve enclosure design yielded shear stresses in the two subsequent geometries of 5,100 dynes/cm2 and 1,900 dynes/cm2, respectively. For the third iteration, a region of stasis occurred during the transition between the inlet port and the blood chamber. Further modifications were implemented, including a reduction in port diameters and further smoothing of the port entry region. This eliminated stasis and yielded a maximum shear level of 4,100 dynes/cm2. In conclusion, optimization was achieved through geometric modification of the VAD, thus minimizing adverse flow conditions.