Background: Previously published studies reported benefits of computer-assisted surgery (CAS) in terms of radiographic implant position in TKA, but whether these improvements result in clinically important survival differences or functional differences that a patient might perceive at a minimum 10-year followup remains largely unknown. Questions/purposes: We performed a prospective randomized trial and asked whether CAS (1) improved survival free from aseptic loosening; and (2) demonstrated any clear difference in patient-reported outcomes at latest followup using validated outcome measures at minimum 10-year followup. Methods: Between January 2004 and December 2005, 80 patients scheduled for TKA were randomly assigned either to the CAS group or to the conventional technique group by the Hospital Informatics Department. The patient inclusion criteria were age 20 to 80 years old, weight < 100 kg, and consent to receive a primary knee arthroplasty performed through a medial parapatellar approach by the senior author. The exclusion criteria were a history of prior knee surgery, TKA performed for a posttraumatic indication, or revision knee surgery. The first 80 patients meeting these criteria were included in the study. There were 21 women and 19 men and in each group; mean age was 66 years (range, 58-77 years), and mean body mass index was 27 ± 4 kg/m2. An initial published study using this patient group investigated only differences regarding implant positioning in the coronal and sagittal planes. This is a secondary analysis of patients from the earlier study protocol at a minimum of 10-year followup with different endpoints. Kaplan-Meier survivorship was compared between groups, and functional patient-reported outcome measures (PROMs) were evaluated using the SF-12, Knee Injury and Osteoarthritis Outcome Score (KOOS), Forgotten Joint Score, and the new Knee Society Score. Those PROMs were not available at the time of the original randomized controlled trial and we therefore do not have baseline preoperative values demonstrating that our two groups were comparable. However, our groups were created using strict randomization and were similar in terms of demographic parameters and knee deformities. Our secondary analysis was not powered for survival analysis but had 80% power to detect a difference > 6 points on the SF-12 components and > 6 points out of 100 on the KOOS subscores (published minimal clinically important difference: 8 points) at the p < 0.05 level. Results: With the numbers available, there was no difference between the CAS group and the conventional TKA group in terms of survivorship free from aseptic loosening 10 years after TKA (97%, 95% confidence interval [CI], 95%-99% versus 97%, 95% CI, 95%-99%; p = 0.98). Investigation of the latest followup PROM scores showed no difference between SF-12 scores (respectively, for CAS and control patients, physical SF-12: 72 ± 12 versus 73 ± 13 mean difference 0, 95% CI -3 to 3, p = 0.9; mental SF-12: 75 ± 8 versus 73 ± 10, mean difference 2, 95% CI 0−4, p = 0.3) as well as for all KOOS subscores (all p > 0.1). Forgotten Joint Scores were similar in both groups with 83 ± 4 for CAS and 82 ± 5 for control patients (mean difference 1, 95% CI 0−2, p = 0.2). Finally, the new Knee Society Scores were not statistically different between groups with a mean objective score of 82 ± 13 for CAS patients versus 79 ± 12 for control patients (mean difference 2, 95% CI 0−5, p = 0.5) and a mean subjective score of 83 ± 11 versus 85 ± 12, respectively (mean difference 2, 95% CI 0−5, p = 0.5). Conclusions: Our observations suggest that CAS used for TKA alignment with restoration of a neutral mechanical axis as the goal did not confer any substantial advantage in survivorship, function, or quality of life at 10 years after TKA. Larger studies with longitudinal collection of PROMs for functional assessment and greater numbers to assess survivorship are needed to confirm these findings. Level of Evidence: Level III, therapeutic study.