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PURPOSE Primary vaginal cancer is a rare disease for which treatment has been modeled based on cervical cancer. We report our experience in the use of image-guided adaptive brachytherapy (IGABT) in this indication. METHODS AND MATERIALS Patients treated for vaginal cancer with a combination of external beam radiation therapy and IGABT were identified through electronic search. The Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology recommendations for cervical cancer have been extrapolated with the definition of two clinical target volumes (CTVs) corresponding to the residual disease after external beam radiation therapy (CTVBT), assessed from clinical and imaging findings, and the so-called CTVi, comprising the CTVBT with directional margins and at least the initial disease at diagnosis. RESULTS Twenty-seven patients were identified. MRI was used for brachytherapy guidance in 82% of the cases. An interstitial component was used in 59% of the cases. The D90 CTVBT and D90 CTVi were 73.1 ± 12.8 Gy and 66.6 ± 6.7 Gy, respectively. After a median followup of 40.1 months, nine recurrences in 8 patients were observed of which four were local. Local relapses occurred within the CTVBT. Three-year local control and disease-free rates were 82% and 65%, respectively. At 2 years, the Grade 2-4 gastrointestinal or urinary morbidity accrual rate was 9%. Twelve patients experienced late sexual morbidity, including three patients with Grade 3 stenosis. CONCLUSION IGABT is feasible in vaginal cancer with promising outcomes. Harmonizing the definition of CTVs is required to allow comparisons between experiences and to perform multicenter studies.