The primary objective was to evaluate the safety and tolerability of the new chewable formulation of mebendazole to treat soil-transmitted helminth (STH) infections in children ≤10 years old with the goal of using this formulation in preventive chemotherapy programs and expand treatment to young children who are unable to swallow solid tablets. In this open-label, single-arm, phase 3 study conducted at Pemba Island, Zanzibar, Tanzania, children aged 2 to 10 years (median age: 4 years) were administered a single dose of the mebendazole 500 mg chewable tablet. Safety was assessed 30 minutes after dose and 3 days later. Of the 390 (98%) children who completed the study, 195 (55%) had ≥1 STH infection and 157 (45%) had no infection at baseline. The most common STH infections were Trichuris trichiura (51%), hookworm (16%), and Ascaris lumbricoides (7%). Treatment-emergent adverse events (TEAEs) were experienced by 11% of children. There was no difference in the percentage of children experiencing TEAEs between the age strata of 2-5 years and 6-10 years. Diarrhea was reported only in children aged 2-5 years. No correlation was observed between the type or percentage of AEs and presence or severity of infection. A single dose of mebendazole 500 mg chewable tablet was safe and well tolerated in children aged 2 to 10 years.