In a previous meta-analysis of intracoronary brachytherapy (ICBT) studies, we identified the target tissue at 0.6 to 0.7 mm tissue depth and we developed two models, describing the relationship between dose and ICBT effectiveness. The purpose of the present study was to validate the identified target tissue depth and the developed dose models, using the results of 1) two prospective animal studies with ICBT, 2) a retrospective analysis of animal studies with external beam irradiation and 3) results of recent clinical ICBT trials. ICBT effectiveness in the porcine restenosis studies was quantified as inhibition of neointima proliferation. The results of these studies were correlated with the developed dose-effectiveness model. Finally, the agreement of the restenosis rates of the recent clinical trials with the developed dose-restenosis model was tested. The porcine restenosis studies demonstrated a dose-related inhibition of neointima proliferation. The radiation effectiveness of both prospective studies and the effectiveness of the studies with external beam irradiation demonstrated the best agreement with the developed dose model at a tissue depth of 0.6 mm. Furthermore, the restenosis rates of the recent clinical ICBT studies were in concordance with the developed dose-restenosis model. In conclusion, the current study validated the localization of the target tissue for ICBT at a tissue depth of 0.6 to 0.7 mm as well as the relationship between dose and ICBT effectiveness at this depth. The data provide a rationale for setting a common dose prescription point at 0.6 to 0.7 mm tissue depth.