A completely operator-independent boundary detection algorithm for multigated blood pool (MGBP) studies has been evaluated at four medical centers. The knowledge-based boundary detector (KBBD) algorithm is nondeterministic, utilizing a priori domain knowledge in the form of rule sets for the localization of cardiac chambers and image features, providing a case-by-case method for the identification and boundary definition of the left ventricle (LV). The nondeterministic algorithm employs multiple processing pathways, where KBBD rules have been designed for conventional (CONV) imaging geometries (nominal 45 degrees LAO, nonzoom) as well as for highly zoomed and/or caudally tilted (ZOOM) studies. The resultant ejection fractions (LVEF) from the KBBD program have been compared with the standard LVEF calculations in 253 total cases in four institutions, 157 utilizing CONV geometry and 96 utilizing ZOOM geometries. The criteria for success was a KBBD boundary adequately defined over the LV as judged by an experienced observer, and the correlation of KBBD LVEFs to the standard calculation of LVEFs for the institution. The overall success rate for all institutions combined was 99.2%, with an overall correlation coefficient of r=0.95 (P<0.001). The individual success rates and EF correlations (r), for CONV and ZOOM geometers were: 98%, r=0.93 (CONV) and 100%, r=0.95 (ZOOM). The KBBD algorithm can be adapted to varying clinical situations, employing automatic processing using artificial intelligence, with performance close to that of a human operator.