Background: Alkylating agents, such as cyclophosphamide and ifosfamide, play a major role in the improved survival of children and young adults with bone and soft tissue sarcoma. However, there is still controversy as to their comparative anti-tumour efficacy and possible adverse effects. This is the second update of the first systematic review evaluating the state of evidence on the effectiveness of cyclophosphamide as compared to ifosfamide for paediatric and young adult patients with sarcoma. Objectives: The primary obective was to compare the effectiveness, that is response rate, event-free survival and overall survival, of cyclophosphamide with that of ifosfamide for paediatric and young adult patients with sarcoma. Secondary objectives were to determine effects of these agents on toxicities (including late effects) and quality of life. Search methods: We searched CENTRAL (The Cochrane Library 2015, issue 2), MEDLINE/PubMed (from 1966 to March 2015) and EMBASE/Ovid (from 1980 to March 2015) with prespecified terms. In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trial databases (www.controlled-trials.com; searched June 2015). Selection criteria: Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing cyclophosphamide and ifosfamide for the treatment of different types of sarcoma in paediatric and young adult patients (aged less than 30 years at diagnosis). Chemotherapy other than either cyclophosphamide or ifosfamide should have been the same in both treatment groups. Data collection and analysis: Two authors independently performed the study selection. Main results: No studies meeting the inclusion criteria of the review were identified. Authors' conclusions: No RCTs or CCTs comparing the effectiveness of cyclophosphamide and ifosfamide in the treatment of bone and soft tissue sarcoma in children and young adults were identified. Therefore no definitive conclusions can be made about the effects of cyclophosphamide and ifosfamide in these patients. Based on the currently available evidence, we are not able to give recommendations for clinical practice. More high-quality research is needed.