Abstract:[Objective] To compare the clinical outcomes of non-cemented total knee arthroplasty (TKA) with cemented TKA through a large-scale retrospective analysis. [Methods] A retrospective analysis was conducted on the data of a major U.S. medical records database PearlDiver, covering 103,231 cases of knee osteoarthritis patients who underwent TKA between October 2015 and October 2020. Among them, 17,299 cases received non-cemented TKA, while the remaining 85,932 cases underwent cemented TKA. The medical complications within 90 days after surgery and surgical complications within 2 years after surgery were compared between the two groups. [Results] The non-cemented cohort proved significantly higher than the cemented counterpart in terms of blood transfusion rate within 90 days after TKA [cases (%), 403 (2.3) vs 1 631 (1.9), P<0.001] and readmission rate [case (%), 1 440 (8.3) vs 6 542 (7.6), P<0.001], whereas the former had significantly lower incidence of deep vein thrombosis than the latter [cases (%), 495 (2.9) vs 2 725 (3.2), P=0.032]. There was no significant difference in the incidence of other medical complications such as pneumonia and pulmonary embolism (P>0.05). However, the non-cemented cohort had significantly lower incidence of aseptic prosthesis loosening within 2 years after surgery than the cemented cohort [cases (%), 318 (1.8) vs 1 811 (2.1), P=0.031]. There were no significant differences in the incidence of wound complications, periprosthetic joint infection, joint stiffness, periprosthetic fracture and revision TKA between the two groups (P>0.05). [Conclusion] In term of primary arthroplasty, the non-cemented TKA has significantly higher risk of perioperative blood loss compared with the cemented counterpart, however, the former has relative lower chance of postoperative aseptic loosening of the prosthesis than the latter. There was no significant difference in the risk of periprosthetic joint infection, revision surgery, or other complications between the two types of TKA.