Optimal treatment strategies for natural killer/T-cell lymphoma (NKTCL) patients with stage IV disease have not been well defined. In this prospective phase 2 study, we evaluated the treatment using MEDA (methotrexate, etoposide, dexamethasone and pegaspargase) as induction chemotherapy and autologous hematopoietic stem cell transplantation (Auto-HSCT) for consolidation. Patients with stage IV disease without prior L-asparaginase-based chemotherapy were eligible. Four cycles of MEDA were administered as induction treatment. Patients with complete response (CR, necessary to have complete metabolic remission of PET/CT, negative plasma EBV-DNA and negative EBER staining of bone marrow biopsy tissue) were consolidated by Auto-HSCT. A total of 53 patients were enrolled. The overall response (OR) rate and CR rate after four cycles of MEDA chemotherapy were 75.5% and 56.6%, respectively. Among them, 25 patients underwent Auto-HSCT. The 4-year overall survival (OS) rate and progression-free survival (PFS) rate were 58.0% (95% CI, 43.4%-70.0%) and 43.4% (95% CI, 29.9%-56.1%), respectively. Patients who underwent Auto-HSCT had a 4-year OS rate of 92.0% (95% CI, 71.6%-97.9%) and a 4-year PFS rate of 80.0% (95% CI, 58.4%-91.1%). Grade 3/4 neutropenia and thrombocytopenia occurred in 28.3% and 17.0% of the patients, respectively. MEDA chemotherapy is an effective induction regimen with reduced grade 3/4 hematological toxicities for stage IV NKTCL. Consolidation with Auto-HSCT can be considered as a potential approach to improve the long-term survival of CR patients after induction treatment.