Background Saline-adenine-glucose-mannitol (SAGM) and a variant solution, AS-1, have been used for more than 30 years to preserve red blood cells (RBCs). Reputedly these RBC components have similar quality, although no paired study has been reported. To determine whether differences exist, a paired study of SAGM RBCs and AS-1 RBCs was conducted to identify membrane changes, including microparticle (MP) quantitation and in vitro RBC-endothelial cell (EC) interaction. Study Design and Methods Two whole blood packs were pooled and split and RBCs were prepared (n = 6 pairs). One pack was suspended in SAGM and one in AS-1. Samples were collected during 42 days of refrigerated storage. RBC shape and size and glycophorin A (GPA)+ and phosphatidylserine (PS)+ MPs were measured by flow cytometry. RBC adhesion to ECs was determined by an in vitro flow perfusion assay. Routine variables (pH, hemolysis) were also measured. Results Compared to SAGM RBCs, AS-1 RBCs had lower hemolysis (p < 0.04), lower GPA+ MPs (p < 0.03), and lower PS+ MPs (p < 0.03) from Day 14 onward. AS-1 RBCs had higher (p < 0.02) side scatter from Day 28 onward compared to SAGM RBCs. SAGM RBCs were more adherent to ECs on Day 28 of storage compared to AS-1 RBCs (p = 0.04), but reversed on Day 42 (p = 0.02). Conclusion SAGM RBCs lose more membrane during storage. SAGM RBCs had increased adherence to ECs on Day 28 of storage, while AS-1 RBCs were more adherent on Day 42. The effect of these differences on the function and survival of SAGM RBCs and AS-1 RBCs after transfusion remains to be determined.