Protein A affinity chromatography represents the key initial capture method in monoclonal antibody (mAb) purification. There are three major types of protein A “resin” based on a different matrix chemistries – glass, agarose and synthetic polymer. State of the art resins must offer good specificity, high mass transfer and binding capacity, low non-specific adsorption, low ligand leakage, suitable back pressure under high flow operation, and good chemical stability – particularly during alkaline sanitization. Until now, selecting a protein A resin for bioprocessing applications involved balancing among high specificity, high mass transfer and binding capacity, low non-specific adsorption and ligand leakage, incompressibility, resistance to alkaline condition for sanitization, chemical stability and cost effectiveness. Recent results using new Amsphere A3 versus Polymer H and Agarose show that the Amsphere A3 design minimizes compromise in performance criteria.