Background Takayasu arteritis (TAK) requires long-term immunosuppression. Cyclophosphamide (CTX) is effective but toxic, whereas tocilizumab provides targeted IL-6 inhibition; however, comparative data on efficacy and safety remain limited. Objective To compare the efficacy, safety, and immunological effects of TCZ versus CTX in patients with TAK. Methods This retrospective cohort study included 75 patients with TAK (TCZ, n = 46; CTX, n = 29). Disease activity NIH score, inflammatory markers, complement levels, and lymphocyte subsets were assessed at baseline and at 3, 6, and 12 months. Adverse events were systematically recorded. Results Both treatments significantly reduced inflammatory markers and improved NIH scores over 12 months, with TCZ achieving faster disease activity control at 3 months. Lymphocyte subset analysis showed stable B-cell counts in the TCZ group, whereas CTX was associated with marked B-cell depletion. The TCZ group had a significantly lower incidence of infections than the CTX group (10.9% vs. 31.0%, p = 0.037) and fewer menstrual disorders (p = 0.026). Other adverse events were comparable between groups. No deaths occurred during follow-up. Conclusion TCZ demonstrated comparable or improved disease control with a more favorable safety profile than CTX. Preservation of B-cell–mediated immunity may be associated with the reduced infection risk observed with TCZ, highlighting a potential mechanism underlying its clinical advantage.