Objective To explore the efficacy and safety of daratumumab(DARA) in the treatment of relapsed/refractory multiple myeloma (R/RMM). Methods We retrospectively analyzed 14 patients treated with DARA, who were diagnosed with R/RMM at our hospital during January 2020 to June 2022. The clinical efficacy, progress free survival (PFS), overall response rate (ORR) and safety after treatment were evaluated. Results Total of 14 patients included 8 males and 6 females, in which the median age was 56.5(33-72) years, and the median disease duration was 29.5(10-96) months. The diagnostic classifications were 2 cases of IgA-κ type, 1 case of IgA-λ type, 7 cases of IgG-κ type, 2 cases of IgG-λ type, 2 cases of unsecretory type, respectively. In 14 patients, 5 patients received 2-line therapy in the past, 6 patients received 3-line therapy, and 3 patients received 4-line therapy. All 14 patients completed the first course of DARA treatment and the treatment efficacy was able to be evaluated. Among them, 5 patients achieved hematological complete response (CR), 4 patients achieved very good partial response (VGPR), 2 patients achieved partial response (PR) and 3 patients achieved stable disease(SD). Among them, 13 patients survived, and 1 patient died of lung infection during non-treatment period. The median duration of the disease was 29.5(10-96) months, the median follow-up time was 6(2-14) months, the PFS time was 5(2-12) months, and the ORR was 78.6%. There were no grade Ⅳ adverse reactions during the treatment period. Among them, blood pressure in 1 patient increased and frequent ventricular premature beats occurred in 1 patient. These adverse reactions were both grade Ⅰ adverse reactions., and could be effectively controlled and improved after active treatment. Conclusions R/RMM treated with DARA on the basis of conventional treatment can improve ORR and depth of remission and prolong the PFS of patients, and shows high safety; but its long-term efficacy still needs to be further observed.