Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive right ventricular (RV) enlargement and systolic dysfunction. Implantation of an transvenous cardioverter-defibrillator (ICD) is frequently used to treat ventricular arrhythmias in ARVC but its effect on RV structural and functional changes has not been investigated.  Objective: We studied whether an ICD might affect the rate of RV structure and functional changes in patients with ARVC.  Methods: In a two-center multinational cohort of 46 pts (37±12 years, 50% men) with definite ARVC by revised 2010 Task Force Criteria, we reviewed 3.5±1.6 serial echocardiograms (range 2-11) over a mean follow-up of 6.7±3.5 years. Echocardiographic measurements included RV outflow tract (RVOT) proximal diameter in parasternal long axis (PLAX) and distal diameter in short axis (PSAX), RV-end diastolic area (RVEDA) and fractional area change (FAC). Statistical analysis was performed using t-tests for continuous and chi-squared test for categorical variables. Results: ICDs were present in 29 pts (63%). All pts enrolled at US site were encouraged to have an ICD as compared to the European site (96 vs 24%, p<0.001). In the European site, only those judged to be at high risk underwent included ICD insertion for ventricular arrhythmia (X) and/or for severe RV dysfunction (Y). Patients were evenly matched with respect to age, gender, presence of a desmosomal genetic mutation and baseline medical therapy (Table 1). The mean RVEDA and RVOT PLAX were similar in pts with and without ICDs but baseline RVOT PSAX was higher in the ICD group and FAC was substantially lower (36±10 vs 46±10%, p=0.001). When adjusted for baseline values, there was a nearly 2-fold increase in the rate of annual RVEDA increase (0.9 vs 0.5 cm2/year p=0.235) and a significant increase in rate of annual PLAX enlargement (0.07 vs 0.01 cm/year, p=0.013). All patients with ICDs had 1.2+ T.R. Conclusions: Although ICDs were implanted in pts with lower baseline RV systolic function, after adjustment for baseline values, pts with ICDs had more rapid progression of RV enlargement. We hypothesize that the RV lead with attendant tricuspid regurgitation leads to further deterioration in RV structure and function.