Anti-tumor necrosis factor treatments for inflammatory bowel disease face challenges like primary nonresponse and secondary loss of response, often due to antidrug antibodies that increase drug clearance. The Fc-gamma receptors type3A (FCGR3A) (rs396991) polymorphism affects infliximab pharmacokinetics and immunogenicity. This study investigates its influence on trough levels, anti-infliximab antibody development, and clinical outcomes in Iraqi ulcerative colitis (UC) patients. This single-center study involved patients on maintenance infliximab therapy who were enrolled. Serum infliximab trough levels and anti-infliximab antibodies (antibodies to infliximab) (free and total) were measured using enzyme-linked immunosorbent assay. Genotyping of the FCGR3A rs396991 polymorphism was performed via polymerase chain reaction amplification and Sanger sequencing. The partial Mayo score assessed disease activity. The significance level of statistics was P < .05. Among 43 patients, those with the CC genotype achieved target infliximab trough levels more frequently (55.6%) than AA (21.1%) or AC (0%) genotypes (P = .005). Median infliximab levels were highest in CC carriers (3.41 µg/mL, P = .022). The AC genotype had a significantly higher prevalence of total anti-infliximab antibodies (53.3%) compared to CC (22.2%) and AA (10.5%) groups (P = .02). Logistic regression confirmed the CC genotype positive association with therapeutic drug levels and lower antibody positivity, while the AC genotype correlated with increased immunogenicity. The FCGR3A rs396991 CC genotype is significantly associated with improved infliximab pharmacokinetics and reduced immunogenicity in UC patients. These findings highlight the potential of FCGR3A genotyping to guide personalized therapeutic strategies and optimize clinical outcomes in UC.