Background: Acute myocardial injury (AMJ), assessed by elevated levels of cardiac troponin, is associated with fatal outcome in coronavirus disease 2019 (COVID-19). However, the role of acute cardiovascular (CV) events defined by clinical manifestation rather than sole elevations of biomarkers is unclear in hospitalized COVID-19 patients. Objective: The aim of this study was to investigate acute clinically manifest CV events in hospitalized COVID-19 patients. Methods: From 1 March 2020 to 5 January 2021, we conducted a multicenter, prospective, epidemiological cohort study at six hospitals from Hamburg, Germany (a portion of the state-wide 45-center CORONA Germany cohort study) enrolling all hospitalized COVID-19 patients. Primary endpoint was occurrence of a clinically manifest CV-event. Results: In total, 132 CV-events occurred in 92 of 414 (22.2%) patients in the Hamburg-cohort: cardiogenic shock in 10 (2.4%), cardiopulmonary resuscitation in 12 (2.9%), acute coronary syndrome in 11 (2.7%), de-novo arrhythmia in 31 (7.5%), acute heart-failure in 43 (10.3%), myocarditis in 2 (0.5%), pulmonary-embolism in 11 (2.7%), thrombosis in 9 (2.2%) and stroke in 3 (0.7%). In the Hamburg-cohort, mortality was 46% (42/92) for patients with a CV-event and 33% (27/83) for patients with only AMJ without CV-event (OR 1.7, CI: (0.94–3.2), p = 0.077). Mortality was higher in patients with CV-events (Odds ratio(OR): 4.8, 95%-confidence-interval(CI): [2.9–8]). Age (OR 1.1, CI: (0.66–1.86)), atrial fibrillation (AF) on baseline-ECG (OR 3.4, CI: (1.74–6.8)), systolic blood-pressure (OR 0.7, CI: (0.53–0.96)), potassium (OR 1.3, CI: (0.99–1.73)) and C-reactive-protein (1.4, CI (1.04–1.76)) were associated with CV-events. Conclusion: Hospitalized COVID-19 patients with clinical manifestation of acute cardiovascular events show an almost five-fold increased mortality. In this regard, the emergence of arrhythmias is a major determinant.