There is an increasing interest to develop injectable drug polymeric carriers not recognizable by the body as foreign particles and eliminated very quickly from the bloodstream. A polyethylene glycol (PEG)-coating onto injectable particles showed to reduce either protein adsorption and complement consumption, as a function of the PEG density. In this work we compared the complement rejecting ability of PEG in different conformations coupled to polyisobutylcyanoacrylate (PIBCA) nanoparticles, through the analysis of the residual hemolytic capacity of the human serum after contact with the particles. Nanoparticles were formed by chemical coupling of PEG during emulsion/polymerization of isobutylcyanoacrylate (IBCA). Nanoparticles characterization included an investigation of their surface properties, such as hydrophilicity and conformational mobility of the PEG chains grafted on the nanoparticles surface, and PEG total content. The polymerization kinetics of IBCA in presence of PEG or MePEG were also studied. Complement consumption was observed to be very sensitive to the number of particles in contact with human serum, as well as to the PEG conformation, suggesting PEG configuration could affect the particle exposed surface.