Resection of pulmonary metastases has previously been reported to improve outcome in high grade osteosarcoma (OS) patients with pulmonary metastases. In this study factors influencing survival in OS patients with pulmonary metastases were determined. One hundred ninety seven patients with OS treated at our institution between 1990 and 2008 under the age of 40 were included. Excluded were patients with insufficient follow-up data (n=12) and irresectable primary tumour (n=11). Of the 174 remaining patients, 26 patients had pulmonary metastases at diagnosis and 62 developed pulmonary metastases during follow-up. Twenty-two of 88 patients (25%) also had extra-pulmonary metastases. Almost all patients with primary non-metastatic OS who experienced a relapse within 310 days (first tertile) died of disease, whereas patients with a relapse free interval of more than 310 days (second and third tertiles) have a significantly better overall survival at about 20% (p=0.02). In total, 56 (63.6%) of 88 patients with pulmonary metastases were treated by metastasectomy. The main reason not to perform metastasectomy was irresect-ability by number and site. Patients with irresectable pulmonary metastases had higher numbers of pulmonary nodules (mean of six vs. three nodules) and more frequent bilateral involvement than patients eligible for surgery (p-values respectively 0.002 and 0.06). Independent risk factors determining survival after metastasectomy in multivariate analysis were male sex (p=0.05), higher numbers of pulmonary nodules (p=0.03) and necrotic metastases (p=0.04). Patients undergoing repeated metastasectomies had a similar chance of survival as patients who underwent metastasectomy once. This well-defined cohort of patients with extensive follow-up data enabled us to identify important risk factors determining survival in OS patients with pulmonary metastases. Risk factors determining poor survival after pulmonary metastasectomy were male sex, higher numbers of pulmonary nodules and resection of vital metastases. Furthermore, we demonstrate that even after repeated metastasectomies, curation can be achieved.