Background COPD and cardiovascular disease (CVD) are leading causes of death with overlapping and syndemic pathophysiological interactions. Inhaled triple therapies containing inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA) and long-acting β 2 -agonists (LABA) reduce COPD exacerbation rates and improve lung function versus dual LAMA/LABA therapy. The effect of inhaled triple therapies on combined cardiac and pulmonary ( i.e. , cardiopulmonary) events in people with COPD and elevated cardiopulmonary risk has not been prospectively tested in randomised clinical trials. Methods THARROS is a multinational, event-driven cardiopulmonary outcomes trial evaluating budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) triple therapy versus glycopyrronium/formoterol fumarate dihydrate dual therapy in patients with COPD and elevated cardiopulmonary risk not using ICS-containing maintenance therapy. Eligibility requirements include symptomatic COPD (COPD Assessment Test scores ≥10) without a requirement for prior COPD exacerbations, blood eosinophils ≥100 cells·mm −3 , established CVD or CVD risk based on clinical characteristics, clinical risk scores or imaging-based risk criteria. The composite primary end-point is time to first severe cardiac or COPD event and includes three event types, including severe cardiac events (heart failure acute healthcare visit/hospitalisation, myocardial infarction hospitalisation), severe COPD exacerbations and cardiopulmonary death. Approximately 5000 patients will be randomised to achieve 632 participants with ≥1 primary severe adjudicated cardiopulmonary event. Conclusion This first-of-its-kind cardiopulmonary outcomes trial will determine the effect of BGF on a novel composite end-point comprising severe cardiopulmonary events in a broad COPD population with elevated cardiopulmonary risk not currently using ICS-containing maintenance therapy.