BACKGROUND: The natural history of perimyocarditis (PMY) is not yet completely known. We aimed to analyse the clinical laboratory data of PMY at diagnosis and during follow-up, in order to assess the natural history and prognostic stratification of the disease (including different aetiology). METHODS: We enrolled 62 consecutive patients (men 79%, aged 38 ± 18 years) with PMY (84% idiopathic, 8% autoimmune, 8% infective) from August 2002 to July 2010. The diagnosis has been made according to clinical and laboratory data (significant increase of troponin I in all patients). After at least 1 year (mean follow-up: 1635 ± 298 days), 59 patients (95%) had available data. RESULTS: Chest pain was present in 59 patients (95%), flu-like syndrome in 36 (58%) and pericardial rubs in 15 (24%). None of the patients showed heart failure at presentation. At admission, eight patients (13%) presented mild-moderate left ventricular systolic dysfunction, 13 (22%) showed wall motion abnormalities, and 10 (17%) showed mild pericardial effusion. At 1 year no patients died, developed heart failure or showed abnormal echocardiogram. NSAIDs were the first choice therapy in 61 (98%) patients with clinical resolution in 58 (95%) of them. Seven patients (12%) experienced intermittent recurrences without development of constrictive pericarditis or heart failure. CONCLUSION: This study underlines the benign mid- to long-term outcome of PMY regardless of clinical laboratory characteristics at presentation, different aetiology and possibility of relapses; minimizing the role of endomyocardial biopsy in these specific patients.