Therapeutic hypothermia can improve survival after cardiopulmonary resuscitation (CPR). Coenzyme Q₁₀ (CoQ₁₀) has shown a protective effect in neurodegenerative disorders. Combining mild hypothermia with CoQ₁₀ after out-of-hospital cardiac arrest could provide additional benefit. Forty-nine patients were randomly assigned to either hypothermia plus CoQ₁₀ or hypothermia plus placebo after CPR. Hypothermia with a core temperature of 35 °C was instituted for 24 h. Liquid CoQ₁₀ 250 mg followed by 150 mg t.i.d. for 5 days or placebo was administered through nasogastric tube. Age, sex, premorbidity, cause of arrest, conditions of CPR and degree of hypoxia were similar in both groups; no side-effects of CoQ₁₀ were identified. Three-month survival in the CoQ₁₀ group was 68% (17 of 25) and 29% (7 of 24) in the placebo group. Nine CoQ₁₀ patients vs. five placebo patients survived with a Glasgow Outcome Scale of 4 or 5. Mean serum S100 protein 24 h after CPR was significantly lower in the CoQ₁₀ group (0.47 vs. 3.5 ng/ml).