Human blood plasma and serum pose significant challenges to implanted devices because of highly unfavorable nonspecific protein adsorption on the surface. In this work, we introduce an improved two-step method to immobilize initiator thiols on a gold substrate for the surface-initiated atom-transfer radical polymerization (SI-ATRP) of hydroxypropyl methacrylate (H PM A). We investigate protein adsorption from a single-protein solution. diluted (10%) and undiluted (100%) human blood plasma, and scrum on the poly(HPMA) brushes with different film thicknesses using surface plasmon resonance (SPR) sensors. Silt results show a correlation between antifouling properties and film thickness: that is, the poly(HPMA) brushes exhibit high protein resistance at medium film thicknesses or similar to 25-40 nm (e.g. <0.3 ng/cm(2) for single-protein adsorption and 10% human blood plasma and serum. similar to 24.5 ng/cm(2) for 100% human serum, and similar to 52.8 ng/cm(2) for 100% human plasma at a thickness of similar to 29 nm). With an optimal film thickness and surface roughness, the poly(HPMA) brush also demonstrates its high resistance to fibroblast adhesion. This work provides an alternative surface polymerization approach to preparing effective antifouling poly(HPMA) materials for potential applications in blood-contacting medical devices.