Objectives <p>To evaluate the effectiveness and safety of rituximab (RTX) compared to cyclophosphamide (CYC) in inducing remission with ANCA-associated vasculitis (AAV).</p> Methods <p>This retrospective study included patients admitted to Renji Hospital from January 2017 to December 2023 who received induction treatment with either RTX or CYC. Effectiveness was evaluated by remission rate at month 6 (± 2 months), with additional subgroup analyses. Safety was assessed based on the occurrence of infections within 6 (± 2) months post-immunosuppression. Comparative analyses and logistic regression were performed using the Inverse Probability of Treatment Weighting (IPTW) method to bolster the reliability of the findings.</p> Results <p>A total of 293 patients were enrolled, with 124 treated with RTX and 169 with CYC for remission induction. The IPTW-weighted analysis indicated that patients administered RTX achieved a higher complete remission (CR) rate (41.4% versus 31.3%, Relative Risk [RR] 1.36). Additionally, there was a significant increase in the odds of urinary tract infections (Odds Ratio [OR] 10.20, 95% Confidence Interval [CI] 0.88 to 2.41, <i>p</i> = 0.05) among RTX recipients.</p> Conclusions <p>RTX demonstrates comparable effectiveness to intravenous CYC in inducing remission, with a particularly marked benefit in PR3-ANCA positive patients. However, this treatment is also associated with a higher risk of urinary infection.</p> Clinical Trial Number <p>Not applicable. This is not a clinical trial but a retrospective analysis.</p>