BACKGROUND: Cannula and pump positions are associated with clinical outcomes such as device thrombosis in patients with HeartMate II; however, clinical implications of HVAD (HeartWare International, Framingham, Massachusetts) cannula position are unknown. This study aims to assess the relationship among cannula position, left ventricular (LV) unloading, and patient prognosis. METHODS AND RESULTS: Twenty-seven HVAD patients (60.0 +/- 12.6 years of age and 19 males [70%]) underwent ramp test. Device position was quantified from chest X-ray parameters obtained at the time of the hemodyamic ramp test: (1) cannula coronal angle, (2) pump depth, (3) cannula sagittal angle, and (4) pump area. Lower cannula coronal angle was associated with LV unloading (as measured by smaller LV diastolic dimension and lower pulmonary capillary wedge pressure). Smaller pump area was associated with LV dynamic unloading, as assessed by steeper negative slopes of LV diastolic dimension and pulmonary capillary wedge pressure during incremental rotational speed change. Cannula coronal angle =65 degrees was associated with reduced heart failure readmission rate (hazard ratio, 10.33; P = .007 by log-rank test). CONCLUSION: HVAD cannula and pump positions are associated with LV unloading and improved clinical outcomes. Prospective studies evaluating surgical techniques to ensure optimal device positioning and its effects on clinical outcomes are warranted.