Abstract Background Patients with relapsed/refractory multiple myeloma are at increased risk of infection. Infections during treatment with teclistamab, the first B‐cell maturation antigen‐directed bispecific antibody approved for triple‐class–exposed relapsed/refractory multiple myeloma, was examined in the phase 1/2 MajesTEC‐1 study. Methods Patients ( N = 165) received subcutaneous teclistamab 1.5 mg/kg weekly after a step‐up dosing schedule (0.06 mg/kg and 0.3 mg/kg, each separated by 2–4 days). Patients were monitored frequently for infections; prophylaxis and management were per institutional guidelines. Results At a median follow‐up of 22.8 months (range, 0.3–33.6), infections were reported in 132 patients (80.0%). Grade 3/4 infections occurred in 91 patients (55.2%), including COVID‐19 (21.2%), respiratory infections (19.4%), Pneumocystis jirovecii pneumonia (4.2%), viral infections (4.2%), and gastrointestinal infections (1.2%). Twenty‐one patients died from infections (18 from COVID‐19). Median time to first onset of any‐grade and grade 3 to 5 infections was 1.7 and 4.2 months, respectively. Overall, 70.9% of patients had ≥1 postbaseline immunoglobulin G (IgG) level <400 mg/dL; median time to IgG <400 mg/dL was 1.2 months (range, 0.2–19.8) and 46.1% received ≥1 dose of IgG replacement. Grade 3/4 neutropenia occurred in 65.5% of patients (median time to grade ≥3 neutropenia/febrile neutropenia was 2.3 months [range, 0–18.1]). Conclusion Based on the infection profile of B‐cell maturation antigen–targeted bispecific antibodies such as teclistamab, it is recommended that clinicians and patients remain vigilant for a range of infection types throughout treatment to facilitate prompt intervention. Appropriate screening, prophylaxis, and management of infections, hypogammaglobulinemia, and neutropenia are important. Clinical trial registration NCT03145181/NCT04557098 ( ClinicalTrials.gov ) Plain Language Summary Before starting teclistamab, patients should be up to date with vaccinations (including COVID‐19) and screened for hepatitis B and C and HIV. Teclistamab should not be given to patients with any active infections. Prophylactic antimicrobials should be administered per institutional guidelines. Prophylaxis for Pneumocystis jirovecii pneumonia and herpes simplex/varicella zoster virus is recommended during teclistamab treatment. Close monitoring of infections and immunoglobulin G (IgG) levels should continue throughout teclistamab treatment. IgG replacement (administered every 3–6 weeks) should be used to maintain IgG ≥400 mg/dL. Growth factors should be considered for grade ≥3 neutropenia with infection/fever and grade 4 neutropenia.