Background: Acute coronary syndrome (ACS)-induced posttraumatic stress disorder (PTSD) and clinically significant PTSD symptoms (PTSS) are found in 4 and 12% of patients, respectively. We hypothesized that trauma-focused counseling prevents the incidence of ACS-induced PTSS. Methods: Within 48 h of hospital admission, 190 patients with high distress during ACS were randomized to a single-session intervention of either trauma-focused counseling or an active control intervention targeting the general role of stress in patients with heart disease. Blind interviewer-rated PTSS (primary outcome) and additional health outcomes were assessed at 3 months of follow-up. Trial results about prevalence were compared with data from previous studies on the natural incidence of ACS-induced PTSS/PTSD. Results: Intention-to-treat analyses revealed no difference in interviewer-rated PTSS between trauma-focused counseling (mean, 11.33; 95% Cl, 9.23-13.43) and stress counseling (9.88; 7.36-12.40; p = 0.40), depressive symptoms (6.01, 4.98-7.03, vs. 4.71, 3.65-5.77; p = 0.08), global psychological distress (5.15, 4.07-6.23, vs. 3.80, 2.60-5.00; p = 0.11), and the risk for cardiovascular-related hospitalization/all-cause mortality (OR, 0.67; 95% CI, 0.37-1.23). Self-rated PTSS indicated less beneficial effects with trauma-focused (6.54; 4.95-8.14) versus stress counseling (3.74; 2.39-5.08; p = 0.017). The completer analysis (154 cases) confirmed these findings. The prevalence rates of interviewer-rated PTSD (0.5%, 1/190) and self-rated PTSS were in this trial much lower than in meta-analyses and observation studies from the same cardiology department. Conclusions: Benefits were not seen for trauma-focused counseling when compared with an active control intervention. Nonetheless, in distressed ACS patients, individual, single-session, early psychological counseling shows potential as a means to prevent posttraumatic responses, but trauma-focused early treatments should probably be avoided.