Introduction The inpatient postoperative outcomes of patients with colostomies following primary total knee arthroplasty (TKA) have not been well studied in the literature. The purpose of this study was to analyze how colostomy impacts the immediate postoperative outcomes of TKA. Our null hypothesis is that after correcting for common variables, a colostomy does not predispose patients undergoing TKA to surgical site infections (SSIs) and periprosthetic infections. Methods The National Inpatient Sample database was used to retrieve information on colostomy patients and patients without a colostomy who had undergone primary TKA from 2016 to 2019. Patients with colostomies were matched to a cohort of non-colostomy control groups in a 1:1 propensity score algorithm by age, sex, race, and pertinent comorbidities. Patient demographic characteristics, comorbidities, length of hospital stay (LOS), total hospital charges, and inpatient complications were compared. Results Following propensity score matching, 399 patients with colostomies were compared to 385 patients without a colostomy (control). The colostomy group had a prolonged LOS (3.15 ± 2.67 vs 2.44 ± 3.15 days, p<0.001) compared to the control group. Also, the colostomy group had significantly higher incidences of acute kidney injury (AKI) (6.02% vs 1.56%, odds ratio (OR): 4.04, 95% confidence interval (CI): 1.63-10.00, p<0.001), blood loss anemia (20.55% vs 13.25%, OR: 1.69, 95% CI: 1.16-2.48, p=0.008), and blood transfusions (4.01% vs 0.26%, OR: 16.04, 95% CI: 2.12-121.56, p<0.001). There was no difference in periprosthetic infection, superficial SSI, or deep SSI. Conclusion Patients with colostomies face a notably higher risk of experiencing AKI, blood loss anemia, and blood transfusion requirements during the immediate postoperative period following primary TKA. Despite the perceived risk of postoperative infection in colostomy patients, this patient population is not at an increased risk of developing periprosthetic infection, superficial SSI, or deep SSI following TKA.