Daratumumab and elotuzumab have demonstrated improvements in overall response rates (ORR) and progression-free survival (PFS) in relapsed/refractory multiple myeloma (RRMM). There is a lack of comparative clinical trials and an even larger lack of consensus on the optimal integration of these novel agents into the treatment paradigm. Clinical outcomes were compared retrospectively in 37 patients who received daratumumab before elotuzumab (dara-first,  = 23) and patients who received elotuzumab before daratumumab (elo-first,  = 14). ORR to the first monoclonal antibody was not different (dara-first 56.5% vs. elo-first 64.3%,  = .641). ORR to the second antibody differed when daratumumab was given second compared to when elotuzumab was given second (64.3% vs. 34.8%, respectively;  = .081). Cumulative PFS for elo-first was significantly longer than dara-first (22.67 months vs. 10.5 months, respectively;  = .001). Response rates to daratumumab may be preserved irrespective of sequence. However, response rates to elotuzumab may diminish with prior daratumumab exposure.