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Purpose: This study aims to assess the feasibility and efficacy of high-dose rate (HDR) brachytherapy (BT) administered in a single insertion with 4 treatment sessions for locally advanced cervical cancer and to identify the prognostic factors influencing outcomes. Methods and Materials: We retrospectively analyzed the clinical data of patients with cervical cancer with locally advanced disease (International Federation of Gynecology and Obstetrics 2018 IB-IVB) treated at our institution from January 2014 through December 2021. Each patient received definitive radiation therapy with an external irradiation dosage between 45 and 50.4 Gy along with concurrent chemotherapy. HDR-BT (24 Gy) was prescribed to a high-risk clinical target volume. Results: One hundred thirty-nine patients were included and the HDR-BT program could be fully performed in 136 patients (98%). Over a median follow-up duration of 40.5 months, the 2-year local control (LC), overall survival (OS), and disease-free survival rates stood at 79.4%, 77.7%, and 61.7%, respectively, with 5-year rates at 78.2%, 61.6%, and 55.7%. Multivariate analysis revealed the primary determinant of LC as the tumor's response to external beam radiation therapy as determined via magnetic resonance imaging before BT. Parametrial involvement demonstrated a significant multivariate association with disease-free survival (P = .04). Regarding OS, parametrial invasion (P = .01) and the tumor's response postchemoradiotherapy (P = .02) emerged as significant factors. Regarding chronic toxicities, 18% (25 patients) experienced grade 3 complications. An optimal D2 cc (bowel) threshold of 70 Gy (P = .001) was identified to limit chronic digestive complications of grade 3 or higher. Conclusions: The implementation of single-insertion, 4-session HDR-BT could be performed in 98% of the patients. It yields favorable LC and OS rates, coupled with tolerable toxicity in patients with locally advanced cervical cancer. Response to initial chemoradiotherapy evaluated on pre-BT magnetic resonance imaging is an important prognostic factor and could help to individualize therapeutic strategies.