Purpose. The failure rate of total ankle arthroplasty (TAA) in rheumatoid patients may be higher than in osteoarthritis patients due to the medications used to treat rheumatoid arthritis and the comorbidities associated with this disease. The purpose of this study was to prospectively look at the intermediate-term outcomes of TAA in patients with rheumatoid arthritis and to compare the results to a matched cohort of patients with ankle osteoarthritis undergoing TAA. Method. This study is a prospective, multicentre comparison study of patients two to eight years post-TAA. A cohort of 57 patients with rheumatoid arthritis was identified from the prospective national database of TAAs (RA group). Matched controls were identified in the database using age, type of prosthesis, and follow-up time as matching criteria (OA group). The following data was collected: demographic information, previous and additional surgeries at the time of TAA and major and minor complications including revisions. Generic and disease specific, validated outcome scores collected include the Short-Form 36 (SF36) and Ankle Osteoarthritis Score (AOS). Results. Each group consisted of 42 female and 15 male patients with an average follow-up of four years. The two groups were similar with an average age of 59.55 years (33–82) in the RA group and 58.13 years (36–85) in the osteoarthritis group and an average BMI of 25.77 kg/m2 in the RA group and 27.70 kg/m2 in the OA group. Preoperative AOS scores were similar in both groups: 64.42 for pain and 72.59 for disability in the RA group and 58.39 for pain and 72.37 for disability in the OA group. There was a significant improvement at latest follow-up: 16.64 for pain and 27.03 for disability in the RA group and 11.75 for pain and 22.66 for disability in the OA group. The OA group had a greater improvement in the SF-36 physical component score (29.97 to 41.29 versus 26.88 to 34.82 in the RA group) whereas the RA group had a greater improvement in the mental component score (49.71 to 56.90 versus 48.99 to 52.02 in the OA group). There was a higher rate of additional surgeries, predominantly hindfoot fusions, in the RA group than the OA group (33 versus 13). Revision rates were similar between the two groups with two revisions in the RA group and three in the OA group. There were no major wound complications in the OA group and two in the RA group. Conclusion. Total ankle arthroplasty is a good option for patients with rheumatoid arthritis. A greater number of additional surgeries were required to balance the foot and support the ankle replacement in the rheumatoid patients than in the osteoarthritis patients. Both groups showed similar improvement in a generic quality of life outcome measure (SF36) and a disease specific functional outcome measure (AOS). Revision rates were similar between the groups; however, the patients with rheumatoid arthritis had a higher rate of wound complications