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Introduction: Teclistamab is the first approved B cell maturation antigen × CD3 bispecific antibody with precision dosing for the treatment of triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). We compared the effectiveness of teclistamab in MajesTEC-1 versus real-world physician's choice of therapy (RWPC) in patients from the prospective, non-interventional LocoMMotion and MoMMent studies., Methods: Patients treated with teclistamab from MajesTEC-1 (N = 165) were compared with an external control arm from LocoMMotion (N = 248) or LocoMMotion + MoMMent pooled (N = 302). Inverse probability of treatment weighting adjusted for imbalances in prognostic baseline characteristics. The relative effect of teclistamab versus RWPC for overall response rate (ORR), very good partial response or better (≥ VGPR) rate, and complete response or better (≥ CR) rate was estimated with an odds ratio using weighted logistic regression transformed into a response-rate ratio (RR) and 95% confidence interval (CI). Weighted proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for duration of response (DOR), progression-free survival (PFS), and overall survival (OS)., Results: Baseline characteristics were well balanced between treatment cohorts after reweighting. Patients treated with teclistamab had significantly improved outcomes versus RWPC in LocoMMotion: ORR (RR [95% CI], 2.44 [1.79-3.33]; p < 0.0001), ≥ VGPR (RR 5.78 [3.74-8.93]; p < 0.0001), ≥ CR (RR 113.73 [15.68-825.13]; p < 0.0001), DOR (HR 0.39 [0.24-0.64]; p = 0.0002), PFS (HR 0.48 [0.35-0.64]; p < 0.0001), and OS (HR 0.64 [0.46-0.88]; p = 0.0055). Teclistamab versus RWPC in LocoMMotion + MoMMent also had significantly improved outcomes: ORR (RR 2.41 [1.80-3.23]; p < 0.0001), ≥ VGPR (RR 5.91 [3.93-8.88]; p < 0.0001), ≥ CR (RR 132.32 [19.06-918.47]; p < 0.0001), DOR (HR 0.43 [0.26-0.71]; p = 0.0011), PFS (HR 0.49 [0.37-0.66]; p < 0.0001), and OS (HR 0.69 [0.50-0.95]; p = 0.0247)., Conclusion: Teclistamab demonstrated significantly improved effectiveness over RWPC in LocoMMotion ± MoMMent, emphasizing its clinical benefit as a highly effective treatment for patients with TCE RRMM., Trial Registration: MajesTEC-1, ClinicalTrials.gov NCT03145181 (phase 1) and NCT04557098 (phase 2); LocoMMotion, ClinicalTrials.gov NCT04035226; MoMMent, ClinicalTrials.gov NCT05160584., (© 2023. The Author(s).)