Studies have demonstrated that patients who have experienced acute coronary syndrome (ACS) have an increased risk of developing posttraumatic stress disorder (PTSD) and experiencing worse survival outcomes than those who do not develop PTSD. Nevertheless, the prevalence rates of PTSD following ACS vary widely across studies, and it is noteworthy that in most cases, the diagnosis of PTSD was based on self-report symptom questionnaires, rather than being established by psychiatrists. Additionally, the individual characteristics of patients who develop PTSD after ACS can differ widely, making it difficult to identify any consistent patterns or predictors of the disorder. To investigate the prevalence of PTSD among a large sample of patients undergoing cardiac rehabilitation (CR) after ACS, as well as their characteristics in comparison to a control group. The participants of this study are patients who have experienced ACS with or without undergoing percutaneous coronary intervention and are enrolled in a 3-wk CR program at the largest CR center in Croatia, the Special Hospital for Medical Rehabilitation Krapinske Toplice. Patient recruitment for the study took place over the course of one year, from January 1, 2022, to December 31, 2022, with a total of 504 participants. The expected average follow-up period for patients included in the study is about 18 mo, and currently ongoing. Using self-assessment questionnaire for PTSD criteria and clinical psychiatric interview, a group of patients with a PTSD diagnosis was identified. From the participants who do not have a PTSD diagnosis, patients who would match those with a PTSD diagnosis in terms of relevant clinical and medical stratification variables and during the same rehabilitation period were selected to enable comparability of the two groups. A total of 507 patients who were enrolled in the CR program were approached to participate in the study. Three patients declined to participate in the study. The screening PTSD Checklist-Civilian Version questionnaire was completed by 504 patients. Out of the total sample of 504 patients, 74.2% were men (n = 374) and 25.8% were women (n = 130). The mean age of all participants was 56.7 years (55.8 for men and 59.1 for women). Among the 504 participants who completed the screening questionnaire, 80 met the cutoff criteria for the PTSD and qualified for further evaluation (15.9%). All 80 patients agreed to a psychiatric interview. Among them, 51 patients (10.1%) were diagnosed with clinical PTSD by a psychiatrist according to Diagnostic and Statistical Manual of Mental Disorders criteria. Among the variables analyzed, there was a noticeable difference in the percentage of theoretical maximum achieved on exercise testing between the PTSD and non-PTSD groups. Non-PTSD group achieved a significantly higher percentage of their maximum compared to the PTSD group (P = 0.035). The preliminary results of the study indicate that a significant proportion of patients with PTSD induced by ACS are not receiving adequate treatment. Furthermore, the data suggest that these patients may exhibit reduced physical activity levels, which could be one of the possible underlying mechanisms in observed poor cardiovascular outcomes in this population. Identifying cardiac biomarkers is crucial for identifying patients at risk of developing PTSD and may derive benefits from personalized interventions based on the principles of precision medicine in multidisciplinary CR programs.