Purpose: This study aimed to evaluate the efficacy and safety of tacrolimus as an add-on therapy in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Patients and Methods: This retrospective cohort analysis was conducted using data from CIDP patients in the database of Xuanwu Hospital, Capital Medical University between April 2019 and June 2023. This study compared the efficacy of tacrolimus plus prednisone (T&P) versus prednisone monotherapy (PM) as maintenance immunosuppressive therapy. The primary endpoint was the response rate, defined as >= 1-point improvement in INCAT score, assessed at 3, 6, and 12 months. Secondary endpoints included: (1) I-RODS score changes from baseline to 3, 6, and 12 months; (2) the monthly median daily prednisone dose; (3) relapse rate (INCAT score worsening >= 1 point) in the 12-month follow-up; and (4) adverse event profiles over the 12-month follow-up period. Results: Among 74 screened CIDP patients, 34 (45.9%) were included, with 16 receiving T&P and 18 receiving PM. All patients completed follow-up (median: 1.4 years; range: 1.0-6.5 years). The T&P group demonstrated significantly higher response rates at 3 and 6 months compared to PM, though this difference attenuated by 12 months. I-RODS improvements were significantly greater in the T&P group at all time points. The relapse rate was lower in the T&P group (12.5% vs 33.3%). The T&P group maintained significantly lower prednisone doses from month 2 onward, with higher prednisone discontinuation rates at 12 months (43.8% vs 11.1%; p=0.01). Both groups showed comparable safety profiles, with no serious adverse reactions reported. Conclusion: Tacrolimus plus prednisone therapy demonstrated superior clinical outcomes compared to prednisone monotherapy in CIDP maintenance treatment, including accelerated symptomatic improvement, reduced relapse risk, and facilitated corticosteroid tapering. The combination regimen maintained an acceptable safety profile without serious adverse events, supporting its corticosteroid-sparing role in CIDP management.