Purpose: This retrospective study aims to compare surgical outcomes between two cohorts of patients who underwent total ankle arthroplasty (TAA) using either standard technique or patient-specific instrumentation (PSI). Methods: A consecutive series of patients who affected of end-staged ankle osteoarthritis were retrospectively assessed and divided into two groups based on TAA techniques: a TAA standard technique group and a TAA-using PSI group. The two groups were compared in terms of operative time, additional procedures, complications (neurovascular and wound problems, infection, loosening and osteolysis, revision and explantation rates, and perioperative fracture), clinical scores, and range of motion (ROM). Result: Fifty-one patients underwent standard TAA, while 13 patients underwent TAA with PSI. At 1-year follow-up, there were no significant differences in complication rates between the two groups (p > 0.05). AOFAS scores were similar, with the standard TAA group scoring 83.33 ± 7.55 and the PSI group scoring 82.92 ± 9.7 (p = 0.870). Likewise, the postoperative ROM did not differ significantly, with 15.12 ± 7.6 degrees for the standard TAA group and 16.05 ± 6.7 degrees for the PSI group (p = 0.689). However, the standard TAA group experienced significantly longer operative time (107.1 ± 22.1 min) compared to the PSI group (91.92 ± 22.9 min, p = 0.032). Additionally, the standard TAA group required more adjunctive procedures (29.7%) compared to the PSI group (7.7%, p = 0.04). Residual pain was also more frequently reported in the standard TAA group (62.7%) than in the PSI group (30.7%, p = 0.038). Conclusion: While both techniques resulted in comparable complication rates, clinical scores and ROM, the PSI group reported significantly shorter operative time and less residual pain, thus requiring fewer postoperative procedures.