Prostate cancer (PCa) is one of the most prevalent diseases in the North American elderly population. Moreover, many patients undergo prostate resection without further treatment and are often considered cured. As such, it is expected that many undergo total knee arthroplasty (TKA) for osteoarthritis while having a history of PCa. Nonetheless, limited research is available on this topic, and without it, surgeons may not be aware of increased complication rates. Therefore, the purpose of this study was to evaluate whether patients at a national level with a history of PCa are at increased risk for complications after TKA. A retrospective case-control, comorbidity matched paired analysis was performed. Patients were identified based on International Classification of Diseases, Ninth Revision codes and matched 1:1 ratio to age, smoker status, chronic kidney disease, diabetes, chronic lung disease, smoking status, and obesity. Patients with active disease were excluded. The 90-day outcomes of TKA were compared through univariate regressions (odds ratios [ORs] and 95% confidence intervals). A total of 2,381,706 TKA patients were identified, and after matching, each comprised 113,365 patients with the same prevalence of the matched comorbidities and demographic characteristics. A significant increase in thromboembolic events that was clinically relevant was found in pulmonary embolisms (PEs) (1.44 vs. 0.4%, OR: 3.04,  < 0.001), Moreover, an increased rate of deep vein thromboses was also seen but was found to be not clinically significant (2.55 vs. 2.85%, OR: 1.19). Although length of stay and other complications were similar, average reimbursements were higher for those with a history of PCa. In conclusion, a history of prior PCa carries significant risk as these patients continue to develop increased PE rates during the 90-day postoperative period which appears to lead to greater economic expenditure. Surgeons and payers should include this comorbidity in risk and patient-specific payment models.