Background & Aims: There is limited data regarding the development of anti-drug antibodies (ADAs) to anti-tumor necrosis factor (TNF) agents in the pediatric population of inflammatory bowel disease (IBD). We aimed to investigate factors associated with the development of immunogenicity to anti-TNF agents in pediatric IBD patients. Methods: This study was a cross-sectional study conducted at the Department of Pediatrics of Kyungpook National University Children’s Hospital. We obtained sera from 59 patients who were under maintenance treatment with infliximab (IFX) or adalimumab (ADL), and ADA levels as well as anti-TNF drug trough levels (TLs) were checked by commercial enzyme-linked immunosorbent assay kits. ADA ＞10 AU/mL was defined as ADA positive, and sub-therapeutic TLs for IFX and ADL were defined as 3 and 5 μg/mL, respectively. Factors associated with ADA positivity were investigated by analyzing clinicodemographic, laboratory, and treatment related factors. Results: Among the 59 patients [49 with Crohn’s disease (CD), and 10 with ulcerative colitis (UC)], 48 and 11 patients were under treatment with IFX and ADL, respectively. ADAs were positive in 6 patients (10.2%). Comparison between ADA positive and negative patients revealed statistically significant differences in white blood cell (WBC) counts (median 8300 vs. 6210 /μL, P=0.001), and the proportion of patients with sub-therapeutic TLs (17% vs. 83.3%, P=0.001). According to multivariable logistic regression analysis, diagnosis with UC and WBC counts (*10sup＞-3/sup＞) were independently associated with the development of ADAs (OR=10.48, 95% CI 1.14-132.07, P=0.042 and OR=2.58, 95% CI 1.42-5.89, P=0.006, respectively). According to receiver operating curve analysis, the optimal cut-off level of predicting ADA positivity were 6930 /μL for WBC count (AUC=0.897, 95% CI 0.796-0.997, sensitivity 100%, specificity 73.8%, P0.001), and 3.48 ㎍/mL for IFX TLs (AUC=0.917, 95% CI 0.815-1.000, sensitivity 100%, specificity 76.2%, P0.001), respectively. Conclusions: WBC counts and IFX TLs may predict the development of ADAs during treatment with anti-TNF agents. Further large-scale studies are required in order to clarity whether immunogenicity to anti-TNF agents are more likely to occur in children with UC compared to those with CD.