BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the clinical outcomes of cancer. Nevertheless, their use may lead to myocardial injury. The 2022 European Society of Cardiology cardio-oncology guidelines recommend routine follow-up of troponin level; however, current guidelines do not provide specific protocols for managing elevated troponin levels during ICI therapy. We aimed to describe the real-life assessment of patients treated with ICIs, presenting with an elevated high-sensitivity troponin I (hs-TnI) level following therapy. METHODS: Tel Aviv Sourasky Medical Center has implemented a routine follow-up of hs-TnI level measurement during ICI therapy. We performed a retrospective analysis evaluating the clinical assessment and management of patients presenting with an elevated hs-Tnl level (> 50 ng/L) following therapy. RESULTS: Among 455 patients performing baseline and follow-up hs-TnI measurements, 50 patients (11%) presented with an elevated hs-TnI level (median 159 ng/L; interquartile range 76-362) following ICI therapy. All patients underwent an electrocardiogram, showing changes in 5 patients (10%). Among 24 patients (48%) who received echocardiography, 4 (8%) showed abnormalities. A cardiology consultation was ordered for 17 patients (34%), and none received cardiac magnetic resonance imaging or coronary angiography. A total of 13 patients (26%) were diagnosed with probable or possible myocarditis, resulting in corticosteroid therapy and discontinuation of ICI therapy in 84% and 92% of the patients, respectively. Only 2 patients reinitiated ICI therapy at a later stage. CONCLUSIONS: We describe for the first time the management of elevated hs-TnI levels following ICI therapy, which was diagnosed in routine serial surveillance. We found a wide diversity in management, low cardiology involvement, and high interruption of therapy, emphasizing the need for standardized protocol management guidelines.