PURPOSE: A prospective phase 2 study was conducted to evaluate the feasibility and safety of single-application multifractionated (SA-MF), high-dose-rate (HDR), image guided adaptive brachytherapy (IGABT) for cervical cancer. METHODS AND MATERIALS: Patients (N = 41) with International Federation of Gynaecology and Obstetrics 2009 stage IIB-IVA disease recruited between 2017 and 2019 underwent SA-MF. After completion of external beam radiation therapy of 50 Gy in 25 fractions, patients received magnetic resonance IGABT. The IGABT protocol consisted of a single brachytherapy (BT) application and treatment with 3 fractions of HDR (9 Gy on day 1; 2 fractions of 7 Gy with a minimum 6-hour gap on day 2) after achieving planning aims of the high-risk clinical target volume (HRCTV) receiving >84 Gy EQD2 and 2 cm3 of the bladder and rectum/sigmoid receiving ≤85 Gy and <71 Gy, respectively. Interfraction variation was addressed by performing computed tomography planning and coregistration using a mutual information-based coordinate system on day 2 before the second fraction. Organ at risk contouring was done on computed tomography, and doses were re-evaluated and reoptimized if required. RESULTS: Thirty-eight patients were treated as per the protocol. All patients underwent Intracavitary + Interstitial BT with needles (median, 4; range, 3-11). The mean ± standard deviation HRCTV volume was 41 ± 21 cm3 and HRCTV D90 dose was 87.2 ± 3.6Gy. The 0.1 cm3 and 2 cm3 to bladder, rectum, and sigmoid were -103.2 ± 10.6 Gy and -84.6 ± 6.8 Gy, 82.2 ± 9.5 Gy and -68.3 ± 5.7 Gy, and 83.5 ± 9.8 Gy and -69.5 ± 5.9 Gy, respectively. Six patients required reoptimization before the second fraction to meet planning aims. Mean overall treatment time was 47 ± 6 days. With a median follow up of 22 months (range, 2-37), 2-year local control and disease-free and overall survival were 90.1%, 85%, and 94.5%, respectively. So far 1 patient with grade II and 2 patients with grade III rectal toxicities have been reported. CONCLUSION: Magnetic resonance IGABT with SA-MF BT was feasible in 95% of patients. The dosimetric parameters and clinical results achieved so far look promising.