Dalbavancin is a lipoglycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections. However, several studies suggested that it is mostly used for off-label indications. This prospective, observational, multicenter study conducted in France from September 2018 to April 2020 aimed to describe the use of dalbavancin in patients who received at least 1 dose of the antibiotic. The primary outcome was the clinical response at 30 days after the last dalbavancin dose. A total of 151 patients in 16 centers were included in this study. The main infection sites were bone and joint infections (55.0%), multisite infections (15.9%), and vascular infections (14.6%), and the primary pathogens were coagulase-negative staphylococci (N=82), Staphylococcus aureus (N=51), and enterococci (N=27). Most patients (71.5%) received 3 previous antibiotic treatments. The number of dalbavancin injections per patient was 1 in 26 patients (17.2%), 2 in 95 patients (62.9%), 3 in 17 patients (11.3%), and more than 3 in 13 patients (8.6%), with a mean cumulative dose of 3,089 ± 1,461 mg per patient. Among the 129 patients with a complete follow-up, clinical success was achieved in 119 patients (92.2%). At least 1 adverse event was reported in 67 patients (44.4%), including 12 (7.9%) patients with dalbavancin-related adverse events. The results of the study showed that dalbavancin is mostly used for off-label indications and in heavily pre-treated patients in France. The clinical response at 30 days after the last dose was favorable in most patients, with a good safety profile. identifier: NCT03726216.