<p>Tofacitinib, a Janus kinase (JAK) inhibitor approved in 2012, has become a pivotal oral treatment for rheumatoid arthritis (RA). However, the risk of venous thromboembolism (VTE) with tofacitinib in RA patients remains uncertain. This study aims to assess the association between tofacitinib use and the risk of VTE events in patients with RA using data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Additionally, this analysis sought to compare the reporting odds ratio (ROR) of VTE associated with tofacitinib and tumor necrosis factor inhibitors (TNFi). We conducted a retrospective pharmacovigilance study using FAERS data from the first quarter of 2012 to the fourth quarter of 2024. Disproportionality analysis was performed using ROR to evaluate the reporting risk of VTE events associated with tofacitinib compared with TNFi agents. A total of 1,786,456 adverse event reports related to RA were identified. Among these, 635 VTE events were associated with tofacitinib use and 1,354 VTE events were associated with TNFi agents. Tofacitinib was associated with a significantly elevated risk of VTE compared with the overall FAERS database (ROR 1.56, 95% CI 1.43–1.70) and with TNFi (ROR 2.20, 95% CI 2.00–2.40). Subgroup analysis revealed that the increased risk was particularly notable for pulmonary embolism (PE) (ROR 1.90, 95% CI 1.69–2.12) and deep vein thrombosis (DVT) (ROR 1.36, 95% CI 1.16–1.59). In this real-world study, tofacitinib use was associated with a higher reporting risk of VTE events compared with TNFi in RA patients. These findings underscore the need for careful patient selection and risk assessment when prescribing tofacitinib. Further prospective studies are warranted to confirm these associations and explore the underlying mechanisms.</p>