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Background: Use of cementless TKA has grown after encouraging data from contemporary implants. Yet registry studies have shown inferior survivorship of cementless fixation when treated as a monolithic class aggregating contemporary and historic designs. Two contemporary cementless TKA designs with distantly different fixation strategies have emerged in the last 2 decades, mostly focused on tibial fixation: porous tantalum and twin-peg tibia and, more recently, porous titanium and a spikes-and-keel tibia. However, their survivorship in comparison with cemented options and between each other remains to be thoroughly delineated., Questions/purposes: (1) Is there a difference in aseptic survivorship between cementless twin-peg TKA constructs compared with cemented options? (2) Is there a difference in aseptic survivorship between cementless spikes-and-keel TKA constructs compared with cemented options? (3) Is there a difference in aseptic survivorship between cementless twin-peg TKA constructs compared with cementless spikes-and-keel TKA constructs?, Methods: We conducted a cohort study using data from the Kaiser Permanente Total Joint Replacement Registry (TJRR). The TJRR prospectively collects patient, perioperative, and implant details on all patients who undergo TKA in a multiregional organization with 12 million members; patients included in the TJRR are longitudinally monitored for outcomes after TKA, and identified outcomes are manually validated through chart review. Patients who underwent primary TKA for osteoarthritis from 2009 to 2023 with a fully cementless construct of either twin-peg or spikes-and-keel, and their fully cemented options, were included (n = 136,443). TKA with hybrid or unknown fixation (2.6% [3571]), rotating or unknown mobility (0.8% [1081]), or fully constrained or unknown stability (1.1% [1549]) were excluded. The final study sample included 130,242 primary TKAs performed by 388 surgeons at 60 hospitals. Of the 125,414 patients receiving twin-peg TKAs, 9.2% who received cemented and 12.3% who received cementless were lost to follow-up. Of the 4828 patients receiving spikes-and-keel TKAs, 11.3% who received cemented versus 11.2% who received cementless were lost to follow-up. Those who terminated membership during the study period tended to be younger than those who did not (65 versus 68 years for both groups). A comparison between cementless (575 twin-peg and 1574 spikes-and-keel) versus cemented (124,839 twin-peg and 3254 spikes-and-keel) fixation was performed for each pair of analogous implants. For the twin-peg comparison, when comparing the cementless group to the cemented group, the cementless group was younger (61 versus 68 years), included more male patients (77% versus 39%), and more patients who self-reported White race (76% versus 66%). For the spikes-and-keel comparison, when comparing the cementless group to the cemented group, the cementless group was younger (65 versus 70 years), had a higher BMI (32 versus 31 kg/m2), included more male patients (47% versus 29%), and had a higher proportion of minimally stabilized implants (57% versus 33%). A secondary comparison was performed between the two fully cementless fixation constructs. When comparing the twin-peg to spikes-and-keel cementless groups, the twin-peg group was younger (61 versus 65 years), included more male patients (76% versus 47%), had a higher proportion of those with an American Society of Anesthesiologist (ASA) classification of 1 to 2 (70% versus 44%), and had a higher proportion of posterior stabilized implants (56% versus 43%). Before outcome evaluation, propensity score weights were calculated using multivariable logistic regression models that included patient age, gender, BMI, race, smoking status, ASA classification, implant stability, and operative year as predictors of treatment assignment. After the application of propensity score weighting, all factors were balanced between the comparison groups except for male gender for the cementless versus cemented twin-peg comparison and twin-peg versus spikes-and-keel cementless comparison. Propensity score-weighted Cox proportional hazards regression was used to evaluate aseptic revision risk of the TKA construct during follow-up for all comparisons. A secondary adjustment was applied in the regression model for male gender as balance was not achieved after propensity score weighting alone., Results: In the adjusted analysis for the twin-peg group, cementless fixation had a higher risk of aseptic revision compared with cemented fixation (HR 2.13 [95% confidence interval (CI) 1.30 to 3.50]; p = 0.003). In the adjusted analysis for the spikes-and-keel group, no difference in aseptic revision risk was observed between cementless and cemented fixation (HR 0.94 [95% CI 0.56 to 1.58]; p = 0.82). When directly comparing cementless twin-peg to spikes-and-keel, twin-peg was associated with a higher risk of aseptic revision compared with spikes-and-keel (HR 2.56 [95% CI 1.13 to 5.79]; p = 0.02)., Conclusion: In this large registry-based cohort study, no cementless TKA construct was associated with better implant survivorship compared with their cemented counterpart options. Cementless fixation may continue to evolve and improve, as cementless spikes-and-keel performed better than twin-peg. But given that reliable results have been observed over longer periods with established cemented TKA, at present, the prudent choice remains cemented TKA. Future recommendations may change but require a demonstrable advantage in implant survivorship and outcomes of future cementless constructs over cemented fixation in carefully designed studies., Level of Evidence: Level III, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2025 by the Association of Bone and Joint Surgeons.)