Tranexamic acid (TXA) has been shown to reduce blood loss and transfusion risk in various orthopedic surgeries including shoulder arthroplasty. However, concerns still exist regarding its use in patients with a history of thrombotic events. Using national claims data, we aimed to study the safety of TXA administration in shoulder arthroplasty patients with a history of thrombotic events. We used retrospective national claims data (Premier Healthcare) on 71,174 patients who underwent a total or reverse shoulder arthroplasty between 2010 and 2016. TXA use was evaluated specifically within a subgroup of patients with a history of thrombotic events such as myocardial infarction, deep venous thrombosis, pulmonary embolism, transient ischemic attack, or ischemic stroke. Studied outcomes were blood transfusion need, complications (including acute renal failure, new onset myocardial infarction, deep venous thrombosis, pulmonary embolism, transient ischemic attack, or ischemic stroke), and cost and length of hospitalization. Mixed-effects models measured the association between TXA use and outcomes, separately in patients with and without a history of thrombotic events. Odds ratios (OR) or percent change for continuous outcomes with 95% confidence intervals (CI) were reported. Overall, TXA was used in 13.7% (n = 9735) of patients, whereas 10.5% (n = 7475) of patients had a history of a thrombotic event. After adjustment for relevant covariates, TXA use (compared with no TXA use) in patients without a history of thrombotic events was associated with decreased odds of blood transfusions (OR, 0.48; CI, 0.24-0.98; P = .0444), whereas no increased odds for complications were observed (OR, 0.83; CI, 0.40-1.76; P = .6354). Similar results were observed in patients with a history of thrombotic events. Moreover, in this subgroup, TXA use was associated with a slight reduction in hospitalization cost (-8.9% CI: -13.1%; -4.6%; P < .0001; group median $18,830). Among shoulder arthroplasty patients, TXA use was not associated with increased complication odds, independent of a history of thrombotic events. These findings are in support of wider TXA use.