We report the synthesis and characterization of dendrimer-entrapped gold nanoparticles (Au DENPs)modified by polyethylene glycol (PEG) with enhanced biocompatibility for computed tomography (CT)imaging applications. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5(G5.NH2) modified by PEG monomethyl ether (G5.NH2-mPEG20) were used as templates to synthesize AuDENPs, followed by acetylation of the remaining dendrimer terminal amines to generate PEGylated AuDENPs. The partial PEGylation modification of dendrimer terminal amines allows high loading of Auwithin the dendrimer interior, and consequently by simply varying the Au salt/dendrimer molar ratio,the size of the PEGylated Au DENPs can be controlled at a range of 2e4 nm with a narrow size distribution.The formed PEGylated Au DENPs are water-dispersible, stable in a pH range of 5e8 anda temperature range of 0e50 C, and non-cytotoxic at a concentration as high as 100 mM. X-ray absorptioncoefficient measurements show that the attenuation intensity of the PEGylated Au DENPs is much higherthan that of Omnipaque with iodine concentration similar to Au. With the sufficiently long half-decaytime demonstrated by pharmacokinetics studies, the PEGylated Au DENPs enabled not only X-ray CTblood pool imaging of mice and rats after intravenous injection of the particles, but also effective CTimaging of a xenograft tumor model in nude mice. These findings suggest that the designed PEGylatedAu DENPs can be used as a promising contrast agent with enhanced biocompatibility for CT imaging ofvarious biological systems, especially in cancer diagnosis.