PURPOSE: To present clinical outcomes and dose-volume histogram parameters of three-dimensional image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) in patients with primary or recurrent gynecologic cancer unsuitable for intracavitary brachytherapy (ICB). METHODS AND MATERIALS: Records of 43 women treated between 2001 and 2009 with iridium-192 gynecologic HDR-ISBT boost, using a Syed-Neblett template and inverse planning simulated annealing dose optimization, were reviewed. Median HDR-ISBT dose was 30 Gy, delivered in 4-6 Gy/fraction. Dose-volume histogram parameters recommended by the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology for image-based ICB were analyzed. Total doses were normalized to 2 Gy fractions (biologically equivalent dose in 2 Gy fractions). Local control (LC) and survival were calculated using Kaplan-Meier method. Toxicities were defined according to Common Terminology Criteria for Adverse Events v3.0. RESULTS: There were 34 primary malignancies (cervix = 12, vagina = 15, Bartholin's gland = 5, and vulva = 2) and 9 recurrences. International Federation of Gynecology and Obstetrics stage distribution for primary cancers was I = 2, II = 13, III = 15, and IV = 4. Median followup was 19.3 months (range, 0-92.2). Two-year LC was 87% for primary cancers, and 45% for recurrent cancers, respectively (p = 0.0175). Median V-100, D-90, and D-100 for clinical target volume were 97.6%, 90.2, and 68.7 Gy(10), respectively. Median bladder and rectal D-2 (ce) were 76.6 and 79.5 Gy(3), respectively. Median urethral D-10 was 80.6 Gy3. Twelve patients experienced Grades 3 and 4 late morbidity, but toxicities were transient. Only 2 patients had persistent severe toxicities. A trend toward increased risk for vaginal necrosis was observed with a clinical target volume >84 cc. CONCLUSIONS: HDR-ISBT may achieve good LC in gynecologic cancer unsuitable for ICB, especially in primary malignancies with a 2-year LC rate higher than 85%. Delivery of such high doses has potential advantages but may predispose to adverse effects, reversible in most cases. Crown Copyright (C) 2012 Published by Elsevier Inc. on behalf of American Brachytherapy Society. All rights reserved.