Intracoronary radiation is a promising therapy to decrease restenosis after percutaneous intervention. The aim of this pilot study was to determine the mechanism of intracoronary beta-radiation after balloon angioplasty and stenting in a double-blind placebo-controlled randomized fashion. Twenty-six patients were randomized to either placebo (n = 6) or 3 doses (28, 35 and 42 Gy) of beta-radiation (n = 20) using the Guidant brachytherapy system (27 mm long 32P source wire). Of these, 21 patients underwent post-procedure and 6-month follow-up three-dimensional intravascular ultrasound (IVUS) assessment. Volumetric quantification was performed by means of a semi-automated contour detection system after an ECG-gated motorized pullback IVUS imaging and three-dimensional reconstruction. We compared the volumetric changes (Delta) of total vessel volume (TVV), plaque volume (PV) and lumen volume (LV) after 6 months between placebo (dummy wire) and irradiated patients. In addition, the volume of neointimal hyperplasia was quantified within the stented segments. There was an opposite behavior of TVV and LV change between placebo (DeltaTVV = -24 mm3 and DeltaLV = -42 mm3) and irradiated (DeltaTVV = +18 mm3 and (DeltaLV = +5 mm3) patients. The mean neointimal formation within the stented segment in the irradiated patients (n = 7) was 1.9 mm3 (1.5%). Our results suggest that beta-radiation affects vessel remodeling after percutaneous intervention and inhibit neointimal formation in stented patients.