Abstract Funding Acknowledgements Type of funding sources: None. Background Leadless pacemakers (LPs) were designed to circumvent pocket- and lead-related pacemaker complications. Up to two years after implantation, adequate real-world safety and efficacy have been demonstrated. Because the duration of pacemaker therapy is well over two years, longer-term data is warranted for the net clinical benefit of leadless pacing. Objective Our aim was to evaluate the safety and efficacy of LP therapy on the long-term in a real-world cohort. Methods In this retrospective cohort study, all consecutive patients were included with a first LP implantation (Nanostim LP or Micra VR LP) from December 21, 2012 to December 13, 2016 in 6 Dutch high-volume centers. The primary safety endpoint was the rate of procedure- or device-related major complications at 5-year follow-up. Analyses were performed with and without the Nanostim battery advisory-related complications. The efficacy is described as pacing threshold, impedance and R-wave amplitude over time; changes in these parameters were assessed using mixed models. Results 179 patients were included (117 [65%] male, mean age 79±9 years), of whom 93 (52%) with a Nanostim and 86 (48%) with a Micra LP. Mean follow-up duration was 45±25 months. A total of 46 major complications occurred, of which 8 not advisory-related. The 5-year major complication rate without advisory-related complications was 4.5% (Figure, A). Including advisory-related complications, the 5-year major complication rate was 30.5%. Not advisory-related complications included dislocations (n=3, of which 2 periprocedurally), pericardial effusion (n=1), groin bleeding (n=1), loss-of-capture (n=2) and pacemaker syndrome (n=1). Reinterventions were required in 7/8 (88%), only prolonged hospitalization in 1 (12%; the groin bleeding), and surgery in none. All 8 occurred within 90 days after implantation. Pacing threshold was stable over time (p=0.53), R-wave amplitude increased (p=0.002), and impedance decreased ...