Introduction Human immunodeficiency virus (HIV) is a retrovirus that can cause acquired immunodeficiency syndrome (AIDS). Total knee arthroplasty (TKA) in HIV-positive patients has not been well documented in the current literature. Thus, this study aimed to examine the early postoperative outcomes and complications of HIV-positive TKA patients as compared to TKA patients who are HIV-negative patients by utilizing the National Inpatient Sample (NIS) database. Methods Admissions data for TKA and HIV were analyzed from the NIS database using ICD-10-CM diagnosis codes. An extensive array of preoperative and postoperative variables was compared among HIV positive TKA patients and HIV negative TKA patients. An unmatched analysis and a matched analysis using a 1:1 propensity match algorithm were conducted to compare the two groups. Results The average age of the HIV-positive group was lower than the HIV-negative group (59.0 vs 66.7, p < 0.001). The HIV-positive group had a smaller percentage of females (38.4% vs 61.5%, p < 0.001) and a lower incidence of tobacco-related disorders than the HIV-negative group (10.3% vs 15.8%, p = 0.032). The HIV-positive group had a longer mean length of stay (3.0 days vs 2.4 days, p < 0.001) and a greater mean total charge incurred (90,780.25 vs 64,801.55, p < 0.001). In the unmatched analysis, the incidence of acute renal failure (6.4% vs 2%, p < 0.001), transfusions (3.9% vs 1.5%, p = 0.004), and periprosthetic joint infection (3% vs 1%, p = 0.007) was higher in HIV positive group. The matched analysis showed a higher incidence of acute renal failure group (6.4% vs 0.5%, p = 0.01) and transfusions (3.9% vs 5%, p = 0.01) in the HIV-positive but a statistically insignificant difference in the rate of periprosthetic joint infection (3% vs 1%, p = 0.153). Conclusion HIV/AIDS is associated with an increased incidence of acute renal failure and transfusions, as well as a longer length of stay and higher incurred costs in TKA patients.