Abstract Background The number of leadless cardiac pacemaker (LCP) implantations has increased over the recent years, being more frequently performed in elderly patients with multiple comorbidities. Purpose The aim of this study is to analyze periprocedural complications and outcome of LCP patients according to their comorbidity status. Methods This is a Swiss multi-centre, retrospective cohort study including all consecutive patients implanted with a LCP (Medtronic Micra VR or AV) between 2015 and 2022. Charlson Comorbidity Index (CCI) was determined and patients were divided into two groups: CCI ≤ 5 (low comorbidity) and CCI > 5 (high comorbidity). Periprocedural complications, in-hospital death, and all-cause mortality were assessed. Results A total of 863 patients (median age 81 years (IQR 76 – 86), male sex 65%) were included in the study, of which 58% had a CCI ≤ 5. Baseline characteristics of the 2 groups are summarized in the table. Patients in the high comorbidity group were older male presenting more frequently with ischemic cardiomyopathy, diabetes, chronic obstructive pulmonary disease, moderate to severe chronic kidney disease and malignancies. Urgent implantations were more frequent in the high comorbidity than in the low comorbidity group (65% vs. 50%, p<0.001). Overall periprocedural complication rate was 2.9% (n = 25) without significant differences between the two groups (2.9% in both groups, p = 1.0). Pericardial effusion requiring pericardiocentesis was the most frequent periprocedural complication (n = 8, 0.9%). Median hospitalization was significantly longer (5 vs. 3 days, p<0.001), and in-hospital mortality significantly higher (3.6% vs. 0.6%, p=0.002) in the high comorbidity group. None of the in-hospital deaths was deemed a periprocedural complication. Median follow-up was 15.4 months. As shown in the figure, all-cause mortality was significantly higher in the high morbidity group (HR 2.9, 95%-CI 2.2-3.8, p<0.001) resulting in a mortality of 58% at 3 years. Conclusions LCP implantation in patients with multiple comorbidities was equally safe with similar peri-procedural complication rates as compared to patients with less comorbidities. However, both in-hospital death and all-cause mortality during follow-up were significantly higher in the high comorbidity group, because patients were older and sicker. Given that costs of LCPs are substantially higher than standard transvenous pacemakers, further studies are necessary to assess cost-effectiveness in patients with high comorbidity and reduced life expectancy.Figure - Survival estimate according CCITable - Baseline characteristics