Background <p>Monoclonal antibodies have emerged as effective therapeutic agents for multiple myeloma. However, monoclonal antibody-related cardiovascular toxicity is controversial and a comprehensive evaluation remains scarce.</p> Methods <p>This pharmacovigilance study utilized records for monoclonal antibodies approved for myeloma (including daratumumab, isatuximab, elotuzumab, belantamab mafodotin, teclistamab, elotuzumab, elranatamab and talquetamab) from the FAERS database (January 1, 2016, to December 31, 2024) via OpenVigil 2.1. Cardiovascular events were screened and broadly categorized based on the MedDRA v24.0 into eight standardized MedDRA queries (SMQs). Reporting odds ratio and information Component were utilized to measure disproportionality and potential risk signals.</p> Results <p>A total of 1160 cardiovascular toxicity events were identified from reports listing monoclonal antibodies as the primary suspect. Heart failure was the predominant cardiovascular toxicity associated with daratumumab, elotuzumab, and isatuximab, followed by embolic and thrombotic events. Additionally, daratumumab and isatuximab were linked to an elevated risk of hypertension, while only daratumumab led to increased risk of arrhythmia. Patients experiencing cardiac toxicity were predominantly male and aged ≥ 65 years. Monoclonal antibodies did not increase the risk of cardiomyopathy, pulmonary hypertension, ischemic heart disease, or torsade de pointes/QT prolongation.</p> Conclusion <p>This study identified significant cardiovascular toxicity signals associated with monoclonal antibodies approved for myeloma, underscoring the importance of monitoring heart failure, embolic and thrombotic events, hypertension, and arrhythmia.</p>