Purpose: To evaluate an automated method for the quantification of fat in the right ventricular (RV) free wall on multidetector computed tomography (CT) images and assess its diagnostic value in arrhythmogenic RV cardiomyopathy (ARVC). Materials and Methods: This study was approved by the institutional review board, and all patients gave informed consent. Thirty-six patients with ARVC (mean age 6 standard deviation, 46 years 6 15; seven women) were compared with 36 age-and sex-matched subjects with no structural heart disease (control group), as well as 36 patients with ischemic cardiomyopathy (ischemic group). Patients underwent contrast material– enhanced electrocardiography-gated cardiac multidetector CT. A 2-mm-thick RV free wall layer was automatically segmented and myocardial fat, expressed as percentage of RV free wall, was quantified as pixels with attenuation less than 210 HU. Patient-specific segmentations were registered to a template to study fat distribution. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic value of fat quantification by using task force criteria as a reference. Results: Fat extent was 16.5% 6 6.1 in ARVC and 4.6% 6 2.7 in non-ARVC (P , .0001). No significant difference was observed between control and ischemic groups (P = .23). A fat extent threshold of 8.5% of RV free wall was used to diagnose ARVC with 94% sensitivity (95% confidence interval [CI]: 82%, 98%) and 92% specificity (95% CI: 83%, 96%). This diagnostic performance was higher than the one for RV volume (mean area under the ROC curve, 0.96 6 0.02 vs 0.88 6 0.04; P = .009). In patients with ARVC, fat correlated to RV volume (R = 0.63, P , .0001), RV function (R = 20.67, P = .001), epsilon waves (R = 0.39, P = .02), inverted T waves in V 1 –V 3 (R = 0.38, P = .02), and presence of PKP2 mutations (R = 0.59, P = .02). Fat distribution differed between patients with ARVC and those without, with posterolateral RV wall being the most ARVC-specific area.