The aim of this study is to describe the real-life use of temocillin in bone and joint infections (BJI). We performed a monocentric retrospective study, including all patients treated by temocillin for a BJI due to extended spectrum β-lactamase-producing Enterobacterales (ESBL-E) between 1 January 2015 and 31 December 2022. Outcomes were evaluated at least 3 months after the end of antimicrobial treatment. Clinical cure was defined as the absence of recurrence of BJI during follow-up among patients who completed at least 7 days of temocillin. If the patient discontinued temocillin due to ineffectiveness, the outcome was considered to be unfavourable. Seventeen patients were treated with temocillin for ESBL-E associated BJI during the study period. Infections included osteomyelitis of the foot (7/17; 41.2%), femoral osteomyelitis (4/17; 23.5%), disco-vertebral infections (2/17; 11.8%), total knee prosthesis infections (2/17; 11.8%) and total hip prosthesis infections (2/17; 11.8%). All patients except one ( = 16) had surgical management of the infection. The main bacteria identified were the complex ( = 9) and ( = 5). The median daily dose was 6 g for a median duration of 42 days (IQR 14-42 days). The median duration of follow-up was 12 months (IQR 5.25-14.5). Overall, 12 patients completed at least 3 months of follow-up, and clinical cure was observed in eight of them (8/12; 66.7%). So far, this is the first report of BJI successfully treated with temocillin. This suggests that temocillin may be an alternative to treat BJI involving difficult-to-treat Enterobacterales when oral therapy is not available.