Introduction The aim of this study was to assess the risk of unfavorable outcomes according to the timing of hypotension episodes in cardiac arrest patients. Material & Method This prospectively conducted multicenter observational study included 1373 out-of-hospital cardiac arrest patients treated with 33 °C targeted temperature management (TTM). Unfavorable neurological outcome and the incidence of complications were analyzed according to the timing of hypotension. Result Compared with hypotension before TTM initiation (adjusted hazard ratio (aHR) 1.51), hypotension within 6 h after TTM initiation was associated with an increased risk of unfavorable neurologic outcome (aHR 1.693), and after 24 h of TTM, was connected with decreased risk (aHR 1.277). The risk of unfavorable neurological outcome was gradually reduced over time after TTM initiation. Hypotension, persisting both before and during TTM, demonstrated a greater risk (aHR 2) than transient hypotension (aHR 1.265). Hypotension was correlated with various complications. Differences in lactate levels were persistent, regardless of the initial fluid therapy (p < 0.001). Conclusion Hypotension showed a strong correlation with unfavorable neurological outcome, especially in the early phase after TTM initiation, and complications. It is essential to manage hypotension that occurs at the beginning of TTM initiation to recover cerebral function in cardiac arrest patients.