Patients with acute myocarditis (AM) and desmosomal gene variations (DGV) have an undetermined risk of serious cardiovascular events. This study’s primary objective was to determine whether or not individuals with AM and pathogenic or possibly pathogenetic DGV had an increased risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure. There were a total of 97 individuals included in this retrospective study from 23 hospitals around the world; 36 had AM and DGV (DGV[+]), 25 had AM, but negative gene testing (DGV[-]), and 36 did not have genetics testing for AM. All patients had elevated troponin along with histological or cardiac magnetic resonance (CMR) findings indicative of AM. A total of 86 individuals were followed up on, and any structural or functional abnormalities detected on CMR were reevaluated. The median age was 24 years old, 91.7% presented with chest discomfort, and median left ventricular ejection fraction (LVEF) was 56% on CMR in the DGV(+) AM group (88.9% DSP variations) (P = NS vs. the other 2 groups). Kaplan-Meier curves showed that myocarditis recurrence and ventricular arrhythmias drove the increased risk of the primary endpoint in DGV(+) AM compared to DGV(-) and without genetics testing individuals (62.3% vs. 17.5% vs. 5.3% at 5 years, respectively; P<0.0001). Late gadolinium-enhanced segments were more common in DGV(+)AM on follow-up CMR. Increased risk of cardiovascular complications is seen in people with AM who also have DGV. More prospective research is required to see if genetic testing could help risk stratify people with AM who are now thought to be at low risk.