BACKGROUND: To assess the effect of targeting higher or lower blood pressure during postresucitation intensive care among comatose patients with out-of-hospital cardiac arrest with a history of heart failure. METHODS: The BOX trial (Blood Pressure and Oxygenation Targets After Out-of-Hospital Cardiac Arrest) was a randomized, controlled, double-blinded, multicenter study comparing titration of vasopressors toward a mean arterial pressure (MAP) of 63 versus 77 mm Hg during postresuscitation intensive care. Patients with a history of heart failure were included in this substudy. Pulmonary artery catheters were inserted shortly after admission. History of heart failure was assessed through chart review of all included patients. The primary outcome was cardiac index during the first 72 hours. Secondary outcomes were left ventricular ejection fraction, heart rate, stroke volume, renal replacement therapy and all-cause mortality at 365 days. RESULTS: A total of 134 patients (17% of the BOX cohort) had a history of heart failure (patients with left ventricular ejection fraction, ≤40%: 103 [77%]) of which 71 (53%) were allocated to a MAP of 77 mm Hg. Cardiac index at intensive care unit arrival was 1.77±0.11 L/min·m −2 in the MAP63-group and 1.78±0.17 L/min·m −2 in the MAP77, P =0.92. During the next 72 hours, the mean difference was 0.15 (95% CI, −0.04 to 0.35) L/min·m −2 ; P group =0.22. Left ventricular ejection fraction and stroke volume was similar between the groups. Patients allocated to MAP77 had significantly elevated heart rate (mean difference 6 [1–12] beats/min, P group =0.03). Vasopressor usage was also significantly increased ( P =0.006). At 365 days, 69 (51%) of the patients had died. The adjusted hazard ratio for 365 day mortality was 1.38 (0.84–2.27), P =0.20 and adjusted odds ratio for renal replacement therapy was 2.73 (0.84–8.89; P =0.09). CONCLUSIONS: In resuscitated patients with out-of-hospital cardiac arrest with a history of heart failure, allocation to a higher blood pressure target resulted in significantly increased heart rate in the higher blood pressure-target group. However, no certain differences was found for cardiac index, left ventricular ejection fraction or stroke volume. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03141099.