Pericarditis as a presenting sign of infective endocarditis is rare. Here we describe 2 cases and an additional 19 cases of pericarditis as a presenting sign of infective endocarditis reported during the last 40 y. 71% of patients were young males (mean age 43.2 y). The most commonly reported underlying conditions were diabetes mellitus type 2 (5 patients, 24%), and substance or alcohol abuse (4 patients, 19%). The native aortic valve was the most frequently involved valve. The most common symptoms were fever, cough or dyspnoea, and chest pain. Overt tamponade was diagnosed in 47% of the patients. However, pulsus paradoxus and pericardial friction rub were rare. A heart murmur was heard in 12 patients (57%). Staphylococcus aureus was the most commonly isolated pathogen concomitantly from blood and pericardial fluid. 16 patients (76%) were operated. Six underwent a pericardial procedure, 5 underwent valve replacement, 4 both, and 1 patient was operated for pseudoaneurysm. Mortality rates were 60% and 31% of patients treated with antibiotics alone versus antibiotics and surgical intervention, respectively. In patients presenting with pericarditis with or without cardiac tamponade, the possibility of infective endocarditis should be considered. Optimal therapy should consist of antibiotics and surgical intervention.