Study objective: To evaluate the safety and potential efficacy of a novel degradable polymer film (DPF) designed to act as a 7-day barrier to prevent intrauterine adhesions (IUAs) after hysteroscopic myomectomy. Design: A prospective single-arm, first-in-human clinical study. Setting: Multicenter study involving 6 centers in France, Belgium, and the Netherlands. Patients: Women aged 40 years or older with no plans to conceive who qualified for hysteroscopic myomectomy (at least 1 10-mm type 0, 1, or 2 myoma) and had a sounded length of the uterine cavity (fundus to exocervix) ranging between 6 cm and 9 cm were considered eligible for the study. Interventions: The DPF was inserted after hysteroscopic transcervical myoma resection. The women were followed up by a telephone call at 30 days and second-look hysteroscopy 4 to 8 weeks after the procedure. Measurements and main results: The chosen safety outcome measures were uterine perforation or cervical trauma at the time of the DPF insertion and unexpected fever, pain, or bleeding beyond 48 hours and up to 30 days after insertion, whereas the outcome measure for efficacy was the absence of IUAs on second-look hysteroscopy. A total of 23 women participated in the study. There were no incidents of uterine perforation or cervical trauma at the time of the DPF insertion. There were no reported adverse effects attributable to the DPF. On second-look hysteroscopy, 20 (87%) of the 23 women had no IUAs. Conclusion: The DPF is a novel, easy-to-apply, and acceptable device to prevent IUAs, with very promising initial safety and efficacy data.