Background—The natural history of myopericarditis/perimyocarditis is poorly known and recently published data have presented contrasting data on their outcomes. The aim of the present article is to assess their prognosis in a multicenter, prospective cohort study. Methods and Results—A total of 486 patients (median age 39 years, range 18-83, 300 men) with acute pericarditis or a myopericardial inflammatory syndrome (myopericarditis/perimyocarditis) (85% idiopathic, 11% connective tissue disease or inflammatory bowel disease, 5% infective) were prospectively evaluated from January 2007 to December 2011. The diagnosis of acute pericarditis was based on the presence of 2 of 4 clinical criteria (chest pain, pericardial rubs, widespread ST-segment elevation or PR depression, and new or worsening pericardial effusion). Myopericardial inflammatory involvement was suspected with atipycal ECG changes for pericarditis, arrhythmias, cardiac troponin elevation and/or new or worsening ventricular dysfunction on echocardiography, and confirmed by cardiac magnetic resonance. After a median follow-up of 36 months normalization of LV function was achieved in >90% of patients with myopericarditis/perimyocarditis. No deaths were recorded, as well as evolution to heart failure or symptomatic LV dysfunction. Recurrences (mainly as recurrent pericarditis) were the most common complication during follow-up and were more frequently recorded in patients with acute pericarditis (32%) than myopericarditis (11%) or perimyocarditis (12%; p<0.001). Troponin elevation was not associated with an increase of complications. Conclusions—The outcome of myopericardial inflammatory syndromes is good. Unlike acute coronary syndromes, troponin elevation is not a negative prognostic marker in this setting.