BACKGROUND: Although current guidelines emphasize the importance of social support to the success of left ventricular assist device (LVAD) therapy, few studies examine the influence of the caregiver on patient outcomes or quantify the impact of LVAD caregiving on caregiver outcomes. The purpose of this analysis was to identify patient and caregiver determinants of patient quality of life (QOL) and caregiver strain in response to LVAD therapy. METHODS AND RESULTS: Data on patients receiving LVAD therapy and their caregivers (n=50 dyads) were prospectively collected pre-implantation and 1, 3, and 6 months post-implantation. Growth curve modeling was used to describe change in patient QOL (Kansas City Cardiomyopathy Questionnaire) and caregiver strain (Multidimensional Caregiver Strain Index). Patient QOL improved most in the first month (β=23.22±3.76, P<0.001), followed by gradual gains over 6 months (β=1.90±0.64, P<0.01). Caregivers experienced worsening of strain in the first month (β=4.30±1.42, P<0.01), followed by gradual resolution to pre-implantation levels by 6 months (β=-0.71±0.23, P<0.01). Worse pre-implantation patient symptoms were associated with greater improvement in patient QOL (β=0.53±0.19, P<0.01) but worsening caregiver strain (β=0.15±0.07, P=0.04). Better relationship quality was associated with greater improvement in patient QOL (β=14.39±5.85, P=0.01) and less pre-implantation caregiver strain (β=-9.31±2.28, P<0.001). Nonspousal caregivers experienced less pre-implantation strain (β=-8.60±3.10, P=0.01), and patients with nonspousal caregivers had less improvement in QOL (β=-3.70±1.62, P=0.02). CONCLUSIONS: A combination of patient and caregiver characteristics predicts patient and caregiver response to LVAD therapy. Including caregiver factors in future studies may be helpful in developing interventions that improve patient and caregiver outcomes, together.