Between January 2008 and June 2014, 513,558 primary unilateral, 33,977 bilateral, and 32,494 revision TKA patients met selection criteria. The overall percentage receiving a transfusion was 14.1% for unilateral, 36.3% for bilateral, and 20.0% for revision procedures. Logistic regression showed patients aged >65 years, female gender, Northeastern location, large hospitals, and higher Charlson score to be significantly associated with higher transfusion risk. Although overall risk of transfusion decreased over the study period, patients with Charlson score ≥3 were at 2.27 (primary unilateral), 1.88 (bilateral), and 2.44 (revision) greater odds of transfusion compared with healthy controls (Charlson score = 0). Generalized linear models showed an incremental total hospitalization cost among those receiving a transfusion of $2477, $4235, and $8594, respectively, compared with those without transfusion.