BACKGROUND: There are no published clinical trials comparing dobutamine with milrinone in outpatients with stage D heart failure on continuous inotropes. METHODS AND RESULTS: In a retrospective analysis of 112 inotrope-dependent patients with stage D heart failure who were not transplant candidates at enrollment, we investigated the relationship between choice of dobutamine or milrinone and mortality. Half the patients were on dobutamine (mean dose, 5.4+/-2.5 microg/kg per minute) and half on milrinone (mean dose, 0.4+/-0.2 microg/kg per minute). Those on dobutamine tended to be older (63 years old versus 54 years old), male (86% versus 79%), and fewer had implantable cardioverter-defibrillators (57% versus 74%). During a median follow-up time of 130 days (range, 2 to 2345 days), there were 85 deaths (76% of cohort) and 55 rehospitalizations. Use of dobutamine compared with milrinone was associated with higher all-cause mortality in an unadjusted analysis (hazard ratio [HR], 1.63; 95% CI, 1.06 to 2.52; P<0.03). However, this association was not significant after adjustment for baseline characteristics in the full cohort (N=112; HR, 0.99; 95% CI 0.5 to 1.97; P=0.98) or propensity-matched cohort (N=70; HR, 0.94; 95% CI 0.48 to 1.85; P=0.86). CONCLUSIONS: In this single-center retrospective study, there were no mortality differences between chronic intravenous dobutamine or milrinone in patients with stage D heart failure being discharged from the hospital. The high mortality in this group selected for inotrope dependence warrants careful consideration of all options and priorities for further care.