Background: The number of patients with cardiac implantable electronic devices (CIEDs) receiving radiotherapy (RT) is increasing. The management of CIED-carriers undergoing RT is challenging and requires a collaborative multidisciplinary approach. Aim: The aim of the study is to report the real-world, ten-year experience of a tertiary multidisciplinary teaching hospital. Methods: We conducted an observational, real-world, retrospective, single-center study, enrolling all CIED-carriers who underwent RT at the San Raffaele University Hospital, between June 2010 and December 2021. All devices were MRI-conditional. The devices were programmed to an asynchronous pacing mode for patients who had an intrinsic heart rate of less than 40 beats per minute. An inhibited pacing mode was used for all other patients. All tachyarrhythmia device functions were temporarily disabled. After each RT session, the CIED were reprogrammed to the original settings. Outcomes included adverse events and changes in the variables that indicate lead and device functions. Results: Between June 2010 and December 2021, 107 patients were enrolled, among which 63 (58.9%) were pacemaker carriers and 44 (41.1%) were ICD carriers. Patients were subjected to a mean of 16.4 (±10.7) RT sessions. The most represented tumors in our cohort were prostate cancer (12; 11%), breast cancer (10; 9%) and lung cancer (28; 26%). No statistically significant changes in device parameters were recorded before and after radiotherapy. Generator failures, power-on resets, changes in pacing threshold or sensing requiring system revision or programming changes, battery depletions, pacing inhibitions and inappropriate therapies did not occur in our cohort of patients during a ten-year time span period. Atrial arrhythmias were recorded during RT session in 14 patients (13.1%) and ventricular arrhythmias were observed at device interrogation in 10 patients (9.9%). Conclusions: Changes in device parameters and arrhythmia occurrence were infrequent, and none resulted in a clinically significant adverse event.