Sixty-three patients with LCH (54 adults, 9 children), with unifocal or multifocal bone lesions were treated with indomethacin. All but one patient achieved a response, that was complete in 52% of them. Overall, 5-year reactivation-free survival was 72%, significantly higher in patients treated with indomethacin as first-line (81.7% vs 52.5%; p=0.01); in those who received indomethacin as single agent (80.5% vs 36.5%, p=0.005); and in those with unifocal disease (90.9% vs 48.1%, p=0.003). Our results confirmed the efficacy of indomethacin in bone LCH both as front-line treatment and after reactivations, in localized, or more extended disease, with minimal side effects.