ABSTRACT Background Selective RET-specific tyrosine kinase inhibitors (RET-TKIs) treat RET fusion-positive non-small cell lung cancer (NSCLC), but studies on their cardiovascular toxicities are limited. This study aimed to characterize the cardiovascular toxicities associated with selective RET-TKI in real-world settings. Research design and methods Data from the United States Food and Drug Administration Adverse Event Reporting System database from 1 January 2020 to 30 June 2023, were analyzed. Two disproportionality methods, information component and reporting odds ratio (ROR) were used. Results Both pralsetinib and selpercatinib showed positive signals for hypertension (pralsetinib: ROR: 5.25, 95% CI: 4.40–6.26; selpercatinib: ROR: 2.68, 95% CI: 1.87–3.82). Additionally, pralsetinib showed a positive signal for ischemic heart disease (ROR: 3.92, 95% CI: 2.94–5.23), and selpercatinib for torsade de pointes/QT prolongation (ROR: 2.65, 95% CI: 1.74–4.04). The median time to onset(TTO) of cardiovascular toxicities was 33 days (IQR: 9–73 days) for pralsetinib and 15 days (IQR: 10–50 days) for selpercatinib. The proportion of deaths, life-threatening events, and hospitalizations due to cardiovascular toxicities were 8.57%, 1.19%, and 31.43%, respectively, for total selective RET-TKI. Conclusions Selective RET-TKIs are related to multiple cardiovascular toxicities. Pralsetinib was linked to ischemic heart disease, and selpercatinib to torsade de pointes/QT prolongation and thrombotic events.