['Vascular brachytherapy (VBT) reduces the rate of recurrence of in-stent restenosis (ISR) by inhibiting intimal proliferation. However, the rate of cell proliferation, reflected by the speed of ISR development, is variable in ISR lesions and might influence the responsiveness of ISR to radiation. The aim of this study was to determine the influence of the initial ISR course on the clinical outcome of patients undergoing VBT.', 'In 1165 patients treated for ISR with VBT in the WRIST studies, we determined the time for ISR (time between initial stent implantation and restenosis), the time for VBT treatment (time between stent implantation and VBT), and previous ISR treatment with conventional strategies. Target lesion revascularization (TLR) at 6 months was available in all patients.', 'Previous ISR treatment did not influence the result of VBT (TLR was 17% vs. 16% without previous angioplasty). Time to ISR influences the outcome of patients undergoing VBT; TLR decreased when ISR occurred later. TLR was 18.2%, 16.7%, and 11.1% when time to ISR was <90, 90-2700, and >270 days, respectively, P=.03. Early ISR (time for ISR <90 days) is a factor for radiation failure (OR=2.1, P<.05). In patients with early ISR, TLR is lower when VBT is delayed; TLR was 11% if performed 90 days after stent implantation as compared to 22% if VBT is performed early (<90 days), P<.05.'] Does the initial course of in-stent restenosis influence the response to vascular brachytherapy?