The goal of this study was to examine a new weightless-like radiation protection garment regarding its radiation protection efficacy and to compare it to a conventional two-piece apron suit plus thyroid collar and standard ancillary shields. All measurements were carried out using a clinical angiography system with a standardized fluoroscopy protocol for different C-arm angulations. An anthropomorphic torso phantom served as a scattering body. In addition, an ionization chamber was used to measure the radiation exposure on five different representative heights and at two different positions of an examiner during a typical fluoroscopic-guided intervention. The new weightless-like radiation protection garment and the conventional protection concept showed a mean dose reduction of 98.1% (p < 0.01) and 90.1% (p < 0.01) when compared to no shielding, respectively. By adding ancillary shields to both systems, an average reduction of 99.0% (p < 0.01) and 98.2% (p < 0.01) was found. In addition, the efficacy of both systems varied depending on the height, the C-arm angulation and position of the examiner. Combined with ancillary shields as an overall protection system, the recently introduced weightless-like radiation protection garment showed a significant better radiation protection efficacy when compared to conventional radiation protection measures.