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To investigate the hemodynamic profile associated with different target temperatures and to assess the prognostic implication of inotropic/vasopressor support and mean arterial pressure after out-of-hospital cardiac arrest. There is a lack of information how different target temperatures may affect hemodynamics.Post hoc analysis of a prospective randomized study.Thirthy-six ICUs in 10 countries.Nine hundred twenty patients (97%) with available vasopressor data out of 950 patients from the Target Temperature Management trial randomly assigned patients to a targeted temperature management at 33°C or 36°C.None.Mean arterial pressure, heart rate, and lactate were registered at prespecified time points. The population was stratified according to cardiovascular Sequential Organ Failure Assessment = 4 defining the high vasopressor group and cardiovascular Sequential Organ Failure Assessment less than or equal to 3 defining the low vasopressor group. The targeted temperature management 33 (TTM33) group had a hemodynamic profile with lower heart rate (–7.0 min–1 [95% confidence limit, –8.7, –5.1]; pgroup < 0.0001), similar mean arterial pressure (–1.1 mm Hg [95% confidence limit, –2.3, 0.2]; pgroup = 0.10), and increased lactate (0.6 mmol/L [95% confidence limit, 0.3, 0.8]; pgroup < 0.0001) compared with the targeted temperature management 36 (TTM36) group. A cardiovascular Sequential Organ Failure Assessment score = 4 was recorded in 54% versus 45%, p = 0.03 in the TTM33 and the TTM36 group, respectively. The high vasopressor group carried a 53% mortality rate when compared with a 34% in the low vasopressor group, plog-rank less than 0.0001, with an adjusted hazard ratio of 1.38 (95% CI, 1.11–1.71; p = 0.004). There was no interaction between vasopressor group and allocated target temperature group (p = 0.40). An inverse relationship between mean arterial pressure and mortality was identified (p = 0.0008).Targeted temperature management at 33°C was associated with hemodynamic alterations with decreased heart rate, elevated levels of lactate, and need for increased vasopressor support compared with targeted temperature management at 36°C. Low mean arterial pressure and need for high doses of vasopressors were associated with increased mortality independent of allocated targeted temperature management.