Clinical brain MR imaging registration algorithms are often made available by commercial vendors without figures of merit. The purpose of this study was to suggest a rational performance comparison methodology for these products. Twenty patients were imaged on clinical 3T scanners by using 4 sequences: T2-weighted, FLAIR, susceptibility-weighted angiography, and T1 postcontrast. Fiducial landmark sites ( = 1175) were specified throughout these image volumes to define identical anatomic locations across sequences. Multiple registration algorithms were applied by using the T2 sequence as a fixed reference. Euclidean error was calculated before and after each registration and compared with a criterion standard landmark registration. The Euclidean effectiveness ratio is the fraction of Euclidean error remaining after registration, and the statistical effectiveness ratio is similar, but accounts for dispersion and noise. Before registration, error values for FLAIR, susceptibility-weighted angiography, and T1 postcontrast were 2.07 ± 0.55 mm, 2.63 ± 0.62 mm, and 3.65 ± 2.00 mm, respectively. Postregistration, the best error values for FLAIR, susceptibility-weighted angiography, and T1 postcontrast were 1.55 ± 0.46 mm, 1.34 ± 0.23 mm, and 1.06 ± 0.16 mm, with Euclidean effectiveness ratio values of 0.493, 0.181, and 0.096 and statistical effectiveness ratio values of 0.573, 0.352, and 0.929 for rigid mutual information, affine mutual information, and a commercial GE registration, respectively. We demonstrate a method for comparing the performance of registration algorithms and suggest the Euclidean error, Euclidean effectiveness ratio, and statistical effectiveness ratio as performance metrics for clinical registration algorithms. These figures of merit allow registration algorithms to be rationally compared.