This retrospective observational study evaluated the effectiveness of endoscopic healing (EH) and the durability of infliximab (IFX) in combination with azathioprine (AZA) versus IFX monotherapy in pediatric patients with Crohn's disease (CD). EH was assessed after 1 year of treatment, whereas IFX durability and associated risk factors were evaluated over an extended follow-up period. Data from 108 pediatric patients were analyzed by comparing the EH rates, IFX trough levels (TLs), antibody-to-IFX (ATIs), and IFX durability between the AZA combination therapy (combination therapy group) and IFX monotherapy (monotherapy group) groups. Of the 108 patients who received IFX therapy, 85 (78.7%) received AZA combination therapy, and 23 (21.3%) received IFX monotherapy. The combination therapy group demonstrated superior EH rates (78.6 vs. 33.3%, p < 0.001), higher IFX TLs (4.6 microg/mL vs. 3.9 microg/mL, p = 0.016), lower ATI positivity (25.0% vs. 52.2%, p = 0.025), and prolonged IFX durability than the monotherapy group. Multivariable Cox proportional hazard regression analysis showed that ATI positivity (hazard ratio [HR] 5.33, 95% confidence interval [CI] 1.61-17.60, p = 0.006) and combination therapy with IFX and AZA (HR 0.13, 95% CI 0.03-0.51, p = 0.004) were associated with IFX durability.