The presence of sesame in Western diet is increasing, making its avoidance by sesame-allergic patients more challenging. To report the efficacy and safety of sesame oral immunotherapy (OIT). Sixty patients aged 4 years or older, diagnosed as sesame-allergic on the basis of a positive oral food challenge, were consecutively enrolled into OIT between November 2014 and November 2017. Fifteen patients with sesame allergy, based on a positive oral food challenge or a recent immediate reaction, and a positive skin prick test result or specific IgE, continued sesame elimination and served as observational controls. Immunologic parameters were measured in a subset (OIT, n= 16; controls, n= 11) at the start and end of the study. Fully desensitized patients continued daily consumption of 1200 mg sesame protein and challenged with 4000 mg after more than 6 months. Fifty-three OIT-treated patients (88.4%) were fully desensitized to sesame, compared with 0% of controls. Four additional patients (total 57 of 60= 95%) were desensitized to more than 1000 mg protein. Reactions occurred in 4.7% of hospital doses and 1.9% of home doses. Epinephrine-treated reactions occurred in 16.7% of patients for hospital and 8.3% for home doses. Significant decreases in rSes i 1 IgE (P= .007) and basophil reactivity (P= .001) and increases in sesame and rSes i 1 IgG4 (P= .001) occurred in OIT-treated patients but not in controls. Forty-seven patients desensitized to 4000 mg were evaluated more than 6 months after reaching maintenance. Only mild reactions were reported during maintenance, and all passed the 4000-mg challenge. Sesame-OIT is an effective alternative to sesame avoidance in allergic patients. The potential for adverse events necessitates its performance in specialized centers.