Numerous hypotheses exist to explain observed blood–materials interactions. It is the purpose of this article to test two popular hypotheses, namely, the minimum interfacial free energy hypothesis and the optimum polar/apolar ratio hypothesis. Methacrylate polymers and copolymers were characterized using the captive bubble underwater contact angle method; bulk water content was determined by gravimetric methods; streaming potential measurements were made; and surface roughness and possible particulate contamination were evaluated by reflected light microscopy. In vitro blood tests include whole blood clotting time measurements on polymer-coated tubes; centrifugal force platelet adhesion on polymer-coated coverslips; and a measure of the partial thromboplastin time, Russell's viper venom time (Stypven time), and the prothrombin time of native whole blood exposed to polymer-coated microscope slides. Results suggest that platelet adhesion correlates in the opposite direction of whole blood clotting time and partial thromboplastin time, emphasizing the need for a multiparameter approach to blood–materials testing. Based on these tests the minimum interfacial free energy hypothesis is not supported. In fact, the data suggest the opposite to be true. It is apparent that platelet adhesion can be a misleading indicator of blood compatibility. Neither hypotheses can explain the apparent conflict between the platelet adhesion data and the coagulation time data.