Objective: Depression is an established risk factor for acute coronary syndrome (ACS), with an impact on cardiac prognosis; nonetheless, the literature disagrees on the role played by anxiety. No study has evaluated this relationship in a cardiac population with no history of depression and after their first diagnosis of ACS. The aim of this study is to explore these associations without the confounding role of long-lasting heart disease or psychiatric illnesses. Method: Two hundred sixty-six patients with no history of depression completed the Hospital Anxiety and Depression Scale and the Primary Care Evaluation of Mental Disorder at baseline and at 1, 2, 4, 6, 9, 12, and 24 months follow-up after their first diagnosis of ACS. During the follow-up period, we collected information regarding the major adverse cardiac events. Results: Developing a first-ever depressive episode, in a proportional hazard model, was associated with almost 3 times the risk of a recurrent cardiac event (odds ratio = 2.590, 95% confidence interval [CI] [1.321, 5.078], p = .006). Furthermore, a moderation analysis revealed that increasing levels of baseline anxiety had opposing effects on cardiac outcomes, being protective only in those who did not develop incident depression (B = −0.0824, 95% CI [−0.164, −0.005], p = .048). No dose–response effect between depressive or anxious symptoms and cardiac outcomes emerged. Conclusion: Our results confirm the detrimental effect of depression on cardiac prognosis in a selected population and suggest that anxiety after the first diagnosis of ACS might have different roles depending on the illness’ course. (PsycINFO Database Record (c) 2018 APA, all rights reserved)