Background:In recent years, aspirin has become a popular agent for venous thromboembolism (VTE) prophylaxis following total joint arthroplasty (TJA). Yet patients with a history of VTE are often given more aggressive prophylactic agents because of their increased baseline risk. The purpose of this study was to assess whether aspirin is an effective prophylactic agent in patients with a history of VTE.Methods:This was a single-institution, retrospective cohort study. The electronic clinical records of 36,333 patients undergoing TJA between 2008 and 2020 were reviewed. Data on demographic characteristics, comorbidities, intraoperative factors, and postoperative complications were collected. A propensity score-matched analysis was performed, as well as a multivariate regression analysis to account for confounders.Results:Of the 36,333 patients undergoing TJA, 1,087 patients (3.0%) had a history of VTE and were not receiving chronic non-aspirin. The risk for subsequent VTE was significantly higher (p = 0.03) in patients with a history of VTE (1.4%) compared with patients without prior VTE (0.9%). However, the incidence of VTE was not significantly lower (p = 0.208) in patients with a history of VTE who received aspirin (0.4%) compared with patients who received other VTE prophylaxis (1.5%). Propensity score matching showed no difference in VTE rates between the 2 groups (2.2% compared with 0.55%; p = 0.372). In a regression analysis accounting for VTE risk, the administration of aspirin was not associated with an increased risk for subsequent VTE (adjusted odds ratio, 0.32 [95% confidence interval, 0.02 to 1.66]; p = 0.274).Conclusions:Our findings suggest that, although patients with a history of VTE have an increased baseline risk for subsequent VTE, aspirin may be a suitable VTE prophylaxis in this group of patients.Level of Evidence:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.