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Background Perioperative myocardial injury (PMI) is a common complication following non-cardiac, particularly thoracic, surgery and is associated with increased cardiovascular risk. Although guidelines recommend cardiac biomarker monitoring to detect PMI, its implementation in routine clinical practice remains limited.Objective To evaluate the combined use of high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting major adverse cardiovascular events (MACE) following elective thoracic surgery, and to determine whether NT-proBNP provides incremental prognostic value beyond hs-cTnI alone.Design Multicentre observational cohort study.Setting Conducted between February 2021 and November 2023 in three Spanish tertiary hospitals.Participants Patients aged ≥45 years scheduled for elective thoracic surgery involving lung resection (pneumonectomy, lobectomy, bilobectomy or segmentectomy) under general anaesthesia. Exclusion criteria included urgent or non-thoracic surgery, active infection or sepsis and a history of severe heart failure (ejection fraction <30%).Main outcome measures Combined measurement of hs-cTnI and NT-proBNP at baseline (preoperatively) and at 24 and 48 hours postoperatively.PMI was defined as hs-cTnI ≥45 ng/L at 24 and/or 48 hours or a ≥20% increase from baseline in patients with elevated preoperative concentrations.Results Among 475 patients, PMI occurred in 11.8%. PMI had higher rates of prior stroke (12.5% vs 2.9%; p=0.004), smoking history (85.7% vs 64.0%; p=0.001) and severe renal dysfunction (7.1% vs 0.7%; p=0.001), with similar Revised Cardiac Risk Index distribution. Patients with PMI also had greater postoperative elevations of hs-cTnI and NT-proBNP (p<0.001), longer surgeries (3.5 hours vs 2.7 hours; p<0.001) and more frequent lobectomy/bilobectomy (64.3% vs 50.4%; p<0.001). Robotic-assisted thoracic surgery (RATS) was associated with increased PMI risk (OR 2.29; p=0.019). Among 49 patients (10.3%) with dual postoperative elevation of hs-cTnI and NT-proBNP, cardiovascular comorbidities were common (hypertension 81.6%, smoking history 85.7%, stroke 14.3%), and most procedures were minimally invasive (video-assisted thoracic surgery 61.2%, RATS 24.5%), with a median duration of 3 hours 42 min. MACE occurred in 18.4% of this group, indicating a substantially elevated risk than isolated or no biomarker elevations. At 30 days, patients with PMI had higher MACE (14.3% vs 3.3%; p<0.001), mortality (3.6% vs 0.7%; p=0.049) and new-onset arrhythmias (5.3% vs 0.2%; p<0.001), particularly atrial fibrillation (7.1% vs 1.7%; p=0.011). Dual biomarker elevation was associated with the highest MACE risk (15.2%), representing a twofold to threefold increase over single biomarkers.Conclusions Combined hs-cTnI and NT-proBNP assessment improves perioperative cardiovascular risk stratification beyond ischaemia.Trial registration number NCT04749212