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). 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 30Gy, delivered in 4-6Gy/fraction. Dose-volume histogram parameters recommended by the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology for image-based ICB were analyzed. Total doses were normalized to 2Gy fractions (biologically equivalent dose in 2Gy 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. 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 68.7Gy(10), respectively. Median bladder and rectal D(2)(cc) were 76.6 and 79.5Gy(3), respectively. Median urethral D(10) was 80.6Gy(3). 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 >84cc. 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.