Aim: To investigate the effects of lower versus higher oxygenation targets in adult intensive care unit (ICU) patients with hypoxaemic respiratory failure after cardiac arrest. Methods: Subgroup analysis of the international Handling Oxygenation Targets in the ICU (HOT-ICU) trial which randomised 2928 adults with acute hypoxaemia to targets of arterial oxygenation of 8 kPa or 12 kPa in the ICU for up to 90 days. Here, we report all outcomes up to one year in the subgroup of patients enrolled after cardiac arrest. Results: The HOT-ICU trial included 335 patients after cardiac arrest: 149 in the lower-oxygenation group and 186 in the higher-oxygenation group. At 90 days, 96/147 patients (65.3%) in the lower-oxygenation group and 111/185 patients (60.0%) in the higher-oxygenation group had died (adjusted relative risk (RR) 1.09, 95% confidence interval (CI) 0.92–1.28, p = 0.32); similar results were found at one year (adjusted RR 1.05, 95% CI 0.90–1.21, p = 0.53). Serious adverse events (SAEs) in the ICU occurred in 23% of patients in the lower-oxygenation group and 38% in the higher-oxygenation group (adjusted RR 0.61, 95% CI 0.43–0.86, p = 0.005); the difference was mainly due to more new episodes of shock in the higher-oxygenation group. No statistically significant differences were observed in other secondary outcomes. Conclusion: A lower oxygenation target in adult ICU patients with hypoxaemic respiratory failure after cardiac arrest did not result in lower mortality, but fewer SAEs occurred in this group compared to the higher-oxygenation group. All analyses are exploratory only, large-scale trials are needed for confirmation. Clinical Trial Registry: Clinicaltrials.gov number NCT03174002 (registered May 30, 2017); EudraCT 2017-000632-34 (registered February 14, 2017).