Background It has been reported that vaccination against hepatitis B is less effective among people with Down syndrome than in the general population. We aimed to evaluate the rate of seroconversion to hepatitis B vaccine in children with Down syndrome from Brazil. Methods A total of 120 people with Down syndrome were included. All of them received the vaccine at intervals of 0, 30 and 180 days and serum samples were tested for the presence of antibodies to the hepatitis B surface antigen (anti‐HBs) 30 days after the last dose. Results In the studied group, 58.3% (70/120) were male and 41.7% (50/120) female, with the median age of 5 years (range 2–15 years). Fifty‐eight of 120 (48.3%) developed anti‐HBs after vaccination. No association was found between gender and/or age and vaccine response. Conclusions The low rate of seroconversion in response to hepatitis B vaccine suggests that all patients with Down syndrome immunized against hepatitis B should be followed and monitored by clinicians.