Background: Radiotherapy treatment for cervical cancer (CC) often induces side effects, including inflammation, dryness, dyspareunia. Considering its key role in the healing process, hyaluronic acid (HA) could be useful for the completion of radiotherapy. Objectives: The aim of this work was to evaluate the ability of HA to reduce the onset of side effects due to radiotherapy. Materials and Methods: In total, 180 women undergoing radiotherapy were randomized into two arms: controls and those treated with vaginal suppositories containing low-molecular-weight HA from day 1 of radiotherapy. The study lasted 5 weeks and was characterized by three visits: at baseline (T0), 15 days later (T1), and at the end of the radiotherapy cycle (T2). The onset of side effects, pain, safety, efficacy, acceptability of treatment, and compliance to the therapy were evaluated. Results: Patients in the control arm reported the onset and worsening of all symptoms with a moderate or severe grade at T2, whereas in the treatment arm almost 90% of patients reported the absence of symptoms or a mild grade. All patients in the treatment arm referred a lower intensity of pain on a visual analog scale compared with the control arm at T2 (6.85 ± 0.94 vs. 1.88 ± 1.02). Conclusions: HA was able to help vaginal mucosa healing during radiotherapy in patients with CC.

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