Abstract Background Atrio-ventricular block (AVB) can often be seen in patients undergoing cardiac procedures. Nevertheless, little is known about the histopathological features of new-onset postoperative AVB prior to the clinical manifestation and its prognostic impact. Purpose This study explores the association of first-degree AVB in ECG and postoperative outcome of patients with either preoperative or a new-onset AVB. Furthermore, histopathological features were analyzed to distinguish the characteristics between preoperative and postoperative AVBs compared to no AVB. Methods CAREBANK is a prospective study with atrial biopsies obtained at the time of open-heart cardiac surgery and long-term follow-up focusing on the adverse events. We analyzed preoperative as well as postoperative ECGs derived after index hospitalization (1-18mo) in patients undergoing CABG. The definition of first-degree AVB was PR-interval ≥200ms. The main outcome of interest was follow-up mortality. Histopathological analysis was used to assess the amount of fibrosis, cardiomyocytes, number of nuclei and macrophages. Results Median follow up time was 4.0 (IQR 2.7 – 5.0) years. First-degree AVB was found in 84/373 (22.5%) preoperative ECGs. Altogether 25/289 (8.7%) cases where ECG was available (after excluding preop AVB, atrial fibrillation) developed first-degree AVB after index hospitalization. New-onset first-degree AVB was associated with increased mortality (aHR 4.033 (95-CI% 1.019–15.965, p=0.047). In atrial histopathological analysis, area covered by cardiomyocytes (p=0.033) as well as area covered by nuclei (p=0.047) were smaller in those with new-onset AVB after surgery, but not in those with preoperative first-degree AVB (p=0.692 and p=0.384) as compared with controls, respectively. Similarly, the total area of fibrosis was greater in those with preoperative first-degree AVB (p<0.001), but not in those with postoperative new-onset AVB (p=0.244). When compared with controls, share of CD68 positive macrophages was similar (p=0.073), but anti-inflammatory CD206 positive M2 macrophages were absent in patients with new-onset AVB (p=0.042). Conclusion Patients with new-onset AVB after CABG have increased mortality in the long-term compared to those without. Histopathology identifies marked differences in macrophage populations between those with and without new-onset AVB.