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Objective: Myocardial infarction (MI) results in mental health consequences, including depression and post-traumatic stress disorder (PTSD). The risk and protective factors of such mental consequences are not fully understood. This study examined the relation between MI severity and future mental health consequences and the moderating role of vagal nerve activity. Methods: In a reanalysis of data from the Myocardial Infarction-Stress Prevention Intervention (MI-SPRINT) study, 154 post-MI patients participated. MI severity was measured by the Killip Scale and by troponin levels. Depression and PTSD symptoms were assessed with valid questionnaires, both at 3 and 12 months. Vagal nerve activity was indexed by the heart rate variability (HRV) parameter of the root-mean square of successive R-R differences (RMSSD). Following multivariate analyses, the association between MI severity and distress was examined in patients with low and high HRV (RMSSD = 30 ms). Results: In the full sample, the Killip index predicted post-MI distress only at 3 months, while troponin predicted distress at 3- and 12-months post-MI. However, HRV moderated the effects of the Killip classification; Killip significantly predicted symptoms of depression and PTSD at 3- and 12-months post-MI, but only in patients with low HRV. Such moderation was absent for troponin. Conclusion: MI severity (Killip classification) predicted post-MI depression and PTSD symptoms, but only in patients with low HRV, suggesting that the vagal nerve is a partial protective (moderating) factor in the relation between Killip score and post-MI distress.