Abstract Background High-dose (HD) chemotherapy with melphalan and autologous blood stem cell transplantation (ABSCT) for treatment of symptomatic multiple myeloma (MM) on an outpatient basis has been well established in the USA and Canada, whereas in Germany and Western Europe an inpatient setting is the current standard. We report on a German single-centre program to offer the procedure on an outpatient basis to selected patients. Methods Major requirements included: patients had to have family and/or other caregivers, had to be able to reach the hospital within 45 min and have an ECOG performance score of 0–1. Patients with severe co-morbidities were not included. Results From September 2012 until April 2016, 21 patients with MM stage IIIA were enrolled. All engrafted within the expected time range (median 14 days), and no severe adverse events occurred. 14 patients (67%) had an episode of neutropenic fever and blood cultures were positive in 4 patients (19%). Although rather liberal criteria for hospital admission were applied, 14 patients (67%) were treated entirely on an outpatient basis. Conclusions HD chemotherapy and ABSCT on an outpatient basis is safe and feasible if it is conducted in an elaborate surveillance program. The feedback from patients was very positive, thus encouraging further expansion of the program.