Daratumumab (DARA) has become a standard care for treating patients with multiple myeloma (MM) and light chain (AL) amyloidosis. The subcutaneous (SC) administration of DARA has been demonstrated to be non-inferior to an intravenous formulation. This retrospective study evaluated patients with MM and/or AL amyloidosis who received SC DARA injections at Tochigi Medical Center Shimotsuga (TMC) and Jichi Medical University (JMU). At TMC, the first dose of DARA was administered on an outpatient basis, whereas at JMU, it was generally administered as an inpatient treatment. At TMC, nurses and pharmacists carefully explained the precautions when administering DARA 1 week in advance. DARA was administered by a physician and patients were observed for 6 h after the first dose. Consequently, outpatient DARA administration was associated with a much shorter median total chair time (345 min) than inpatient treatment (median, 7 days). The incidence of administration-related reactions was low (only one patient in each group). The results revealed that, with aggressive premedication and medical cooperation, the first dose of SC DARA can be safely administered in an outpatient setting.