Heavy workload in hospital transfusion services and blood centers necessitates the implementation of automated platforms. We evaluated the performance of Erytra Eflexis (Diagnostic Grifols), a recently developed midsize automated instrument for pretransfusion testing, in comparison with a US Food and Drug Administration (FDA)-cleared device (Erytra). Reproducibility and repeatability of the results were also investigated.Studies were conducted using the same card technology and reagents at three US sites. Tests were performed on 9174 specimens from hospital patients (55.61%) and blood donors (43.39%). Evaluations included 18,413 ABO/D/reverse typing; 9084 Rh phenotypes, 4640 K phenotypes, 2052 antibody screenings, 1232 antibody identifications, 469 direct antiglobulin tests, 612 IgG crossmatches, and 700 ABO-compatibility crossmatches. A reference blood panel was also sent to each center, for a total of 3900 replicate tests. Concordance between results with the two instruments and performance among the different centers were statistically evaluated.Agreement between instruments was 99.84% for 37,202 test results, with 61 discrepancies (0.16%). Percentages of positive and negative agreement were 99.82% and 99.85%, respectively. No discrepancies were observed in 12,276 tests for direct ABO/D grouping. Discrepancies were observed during antibody identification (n = 19), antibody screening (n = 15), and reverse grouping (n = 10). Investigations of the discrepancies were resolved in favor of the study instrument in 55.73% of the cases. Erytra Eflexis obtained the expected results in the reproducibility analysis.This multicenter study demonstrates that Erytra Eflexis with its gel card technology and reagents is reliable and substantially equivalent to the FDA-cleared instrument used as the reference.