Stents are used to treat the 1st and even successive in-stent restenosis (ISR) episodes. In 18 patients (19 lesions), IVUS was performed after de novo stent implantation, after the 2nd stent was used to treat the 1st episode of ISR, and after the 3rd stent was used to treat the 2nd episode of ISR. The duration between the 1st and 2nd stent was 355짹374 days and between the 2nd and 3rd stent was 330짹279 days. The duration of follow-up after the 3rd stent was 307짹145 days. High pressure inflation (>14atm) was performed for 69% (11/16) of patients when treating the 1st episode of ISR and all pts when treating the re-ISR (p=0.013). Results. Vessel area and final minimal stent area (MSA) did not increase with successive re-stenting, and the ratio of minimum stent diameter to nominal stent size suggested that chronic stent underexpansion persisted. MSA >5 mm2 (one accepted criteria for drug-eluting stent underexpansion) was noted in 54% after the 1st stent, 35% after the 2nd stent, and 42% after the 3rd stent (p=0.6). After the 3rd stent, the rate of target lesion revascularization was 29% (5/19) and target vessel revascularization was 10% (2/19); there was 1 non-fatal myocardial infarction. Thus, the overall rate of major adverse cardiac events was 42%. Conclusion. While serial re-stenting a recurrent ISR lesion was not associated with progressive decrease in MSA, it was still associated with chronic stent underexpansion and a high rate of adverse events.