Abstract Objective—To evaluate the diagnostic accuracy of radiographically derived measurements of vertebral heart score (VHS) and sphericity index (SI) in the detection of pericardial effusion (PE) in dogs. Design—Retrospective case-control study. Animals—51 dogs with PE associated with various cardiac disorders, 50 dogs with left- or right-sided cardiac disorders without PE, 50 dogs with bilateral cardiac disorders without PE, and 50 healthy dogs. Procedures—Measurements of VHS on lateral (lateral VHS) and ventrodorsal (ventrodorsal VHS) radiographs, SI on lateral (lateral SI) and ventrodorsal (ventrodorsal SI) radiographs, and global SI (mean of lateral SI and ventrodorsal SI) were obtained. Receiver operating characteristic curves were calculated to evaluate the diagnostic accuracy of the radiographic indexes at differentiating dogs with PE from those with other cardiac disorders without PE. Results—Measurements of lateral and ventrodorsal VHS were significantly higher in dogs with PE, compared with values for all dogs without PE. Measurements of lateral, ventrodorsal, and global SI were significantly lower in dogs with PE, compared with values for all dogs without PE. Cutoff values of > 11.9, > 12.3, and ≤ 1.17 for lateral VHS, ventrodorsal VHS, and global SI, respectively, were the most accurate radiographic indexes for identifying dogs with PE. Conclusions and Clinical Relevance—Cardiac silhouettes of dogs with PE were larger and more rounded, compared with those of dogs with other cardiac disorders without PE. Objective radiographic indexes of cardiac size and roundness were only moderately accurate at distinguishing dogs with PE from dogs with other cardiac disorders without PE.