AbstractBackgroundTo evaluate patient and tumour characteristics, treatment and their impact on survival in patients with a solitary pulmonary metastasis at first relapse of high‐grade osteosarcoma.ProcedureTwo‐hundred and nineteen consecutive patients who had achieved a complete surgical remission and then developed a solitary pulmonary metastasis at first recurrence of high‐grade osteosarcoma were retrospectively reviewed.ResultsTwo hundred and three (94.9%) of 214 patients achieved a second complete remission. After a median time from initial diagnosis of osteosarcoma to first relapse of 2.3 years (range, 0.3–18.8 years), actuarial post‐relapse overall survival after 2 and 5 years was 72.0% and 51.2%. Post‐relapse event‐free survival was 39.1% and 31.1%. Median follow‐up time was 3.2 years (range, 0.1–29.4 years). A longer time until first relapse and diagnosis due to imaging were positive prognostic factors in uni‐ and multivariate analyses, as were a second complete surgical remission and, in regard to death, the absence of a subsequent relapse. The use of salvage chemotherapy and radiotherapy were not associated with patient outcomes, nor was the surgical approach (thoracoscopy vs. thoracotomy) nor the exploration (uni‐ vs. bilateral).ConclusionApproximately half of the patients who experience a solitary pulmonary relapse at first recurrence of osteosarcoma remain alive 5 years after this first relapse. Only one third will remain disease‐free. A complete surgical resection of the lesion is essential for long‐term survival while relapse chemotherapy does not seem to improve survival. Innovative therapies are required to improve outcomes.