Summary Background The cause of pericarditis is manifold. It can occur as a result of various diseases but may also be triggered by drugs. However, the data on drug-induced pericarditis are still scarce. Case report A 64-year-old female hypertensive patient with rheumatoid arthritis for 20 years presented with thoracic pain and recurrent pericardial and pleural effusions. For treatment of the recurrent effusions, the patient received glucocorticoids and colchicine in addition to the basic rheumatoid arthritis therapy, and treatment has only recently been expanded to include etanercept. On admission, she complained of malaise, dysphagia, and blood pressure was 85/55 mm Hg. She was normofrequent with elevated inflammatory parameters. On trans-thoracal echocardiography (TTE) and computer-tomography (CT), there was a 3-cm non-floating structure in the entire circumference of the pericardium. The indication for pericardiectomy was given because of hemodynamic impairment. After incision of the pericardium, 250 ml of a brown-reddish fluid drained, with brown crumbly necrotic masses visible underneath. Histopathologic findings revealed vasculitis-related chronic fibrinous pericarditis with vasculitic changes. A subclinical infection with Staphylococcus aureus was detectable by PCR analysis. Conclusion Based on the fact that tumor necrosis factor blockers can induce vasculitis, etanercept might have been responsible for the exacerbation of pericarditis. The underlying rheumatoid arthritis could also be considered as a trigger. The detection of Staphylococcus aureus DNA in the pericardium and the exacerbation of pericarditis could be attributed to secondary vasculitis after an infection with S. aureus, whereas the tendency to infection due to humoral immunodeficiency after years of immunosuppressive therapy has to be discussed as a trigger.