Abstract Background Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide, particularly in countries with limited access to healthcare [1,2]. Acute coronary syndrome is a collective term for several clinical conditions resulting from narrowing or occlusion of the coronary arteries [3,4]. Another group of patients affected by cardiovascular disease are those who have undergone heart transplantation. Long-term survival after transplantation is limited by cardiac allograft vasculopathy, a condition that affects the coronary arteries of the donor heart and causes diffuse narrowing [5,6]. Our retrospective analysis aims to compare the prognostic outcomes of HTX patients with ACS who underwent PCI with patients without a history of HTX. Results A total of 3194 patients with ACS were enrolled, of whom 1.16% (37) had a previous heart transplant. Patients with prior transplantation were on average younger (52.54 ± 15.13 vs. 69.76 ± 12.16, p < 0.001), had less dyspnea (p < 0.001) and a different distribution of ACS types (p < 0.001), as shown in Figure 1. There were no differences in sex (p = 0.287), BMI (p = 0.123), hypertension (p = 0.557), diabetes mellitus (p = 0.188) and previous myocardial infarction (p = 0.681). The majority of HTX patients were diagnosed with ISHLT CAV III (58.54%) and the average time to PCI was 12 years after transplantation. Multi-vessel disease was more common in HTX patients (p < 0.001). In addition, calcification was less frequent in the HTX group than in the control group (p < 0.001), and the lesion morphology was more diffuse in the HTX group (p < 0.001). On the other hand, there was no difference in the distribution of target vessels (p = 0.424), with the left anterior descending being the most frequently treated coronary artery, followed by the left circumflex and right coronary arteries. HTX patients received more stents (p < 0.001). There was also a difference in post-procedural TIMI flow achieved (p = 0.047), with less TIMI 3 flow achieved after PCI in the HTX group (80% vs. 93.59%). Technical success was less likely to be achieved in the HTX group (62.50% vs. 96.29%, p < 0.001), as was procedural success (47.06% vs. 89.68%, p < 0.001). There was no difference in the incidence of complications, which include perforation and bleeding (p = 0.284). All-cause mortality at three years (39.02% vs. 17.50%, p < 0.001), stroke (7.32% vs. 1.59%, p = 0.035) and myocardial infarction (p = 0.026) were higher in the HTX group. Over a period of three years, MACCE was more likely to occur in the HTX sub-group, which is shown graphically in Figure 2. Conclusion Interventional treatment of ACS in HTX patients is an option with a complication rate comparable to non-HTX patients and with a lower technical and procedural success - partly due to the diffuse nature of CAV and the involvement of distal and microvascular vessels. Overall MACCE and survival are inferior to the control population.Figure 1Figure 2