Thalidomide is a second-line treatment for discoid lupus erythematosus (DLE). The efficacy of this treatment, the minimum effective doses, and safety is poorly documented in the literature. The aim of the study was to determine the efficacy and tolerance of thalidomide as first or second line of therapy for discoid lupus erythematosus. We present a retrospective single-centre study of 68 patients with DLE treated with thalidomide from 2003 to 2019. The inclusion criteria were the presence of clinical lesions suggestive of DLE, confirmed by histological examination and direct immunofluorescence. The mean age at diagnosis was 37.45 years (range 18-65 years). Thalidomide was started an average of 2.25 years after the diagnosis of DLE, as second-line therapy in 85% of the cases (58 patients), and as first-line therapy in 10 patients (15%). Fifty-six patients improved with thalidomide (82%), 39 cases achieved complete remission and 17 partial remissions. The mean duration of follow-up with thalidomide was 8.4 months (range 3-25 months). Five patients discontinued thalidomide due to adverse events. The most frequent side effect was headache (23.5%). Thalidomide is effective and safe in DLE patients as first or second-line treatment with a good safety profile.© 2021 The Australasian College of Dermatologists.