OBJECTIVE Restenosis following percutaneous transluminal renal angioplasty (PTRA) remains a concern even in the era of adjuvant stenting. The optimal form of therapy, and particularly the role of repeat PTRA in the treatment of recurrent hypertension associated with renal artery restenosis, is largely unknown. The aims of this study were to determine the risk factors for restenosis and to evaluate the blood pressure outcomes of patients who underwent repeat PTRA. METHODS Clinical and procedural characteristics of 32 patients who developed recurrent hypertension and renal artery restenosis were compared to a control group of patients who maintained renal artery patency and adequate blood pressure control after the first procedure. The groups were matched for sex and initial procedure date. RESULTS The restenosis group had a mean age of 71 +/- 12 years, a female/male ratio of 24/8, an average blood pressure of 179/87 mm Hg, despite three antihypertensive medications, and a serum creatinine level of 1.5 +/- 0.4 mg/dl. Repeat PTRA performed for clinically significant restenosis was 10.7 +/- 8 months after the first procedure, and 17 of the 32 patients had a measurable blood pressure benefit at last follow-up (177 +/- 119 weeks). The development of restenosis was positively associated with body weight (p = 0.003) and body mass index (p = 0.008), but independent of diabetes mellitus, hyperlipidemia, or statin therapy. Of the 15 patients who failed the second procedure, 4 went on to have third PTRA, none of whom had sustained benefit. CONCLUSIONS An increased body mass index is associated with restenosis following initial PTRA. Patients with restenosis can be treated successfully with repeat PTRA which provides sustained improvement in blood pressure control in approximately half of these patients.