INTRODUCTION: This is the third evaluation study of the hepatitis B virus (HBV) vaccination program, initiated in 1989 in Saudi Arabia. AIMS: This study sought to assess the efficacy and long-term protection of the hepatitis B vaccine among Saudi adolescents. METHODS: School students between the ages of 16 and 18 years were randomly chosen from high endemic (Aseer), intermediate endemic (Madinah), and low endemic (Al-Qaseem) areas of the country. Hepatitis B surface antigen (HBsAg), hepatitis B core IgG antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs) were measured using standard techniques. RESULTS: A total of 1355 students (689 males and 666 females) were selected randomly from the three areas. No cases of positive HBsAg or anti-HBc were detected among the study population. Five hundred and ten students (38%) showed protective anti-HBs titers (>/= 10mIU/ml), while 528 (39%) students had undetectable anti-HBs titers (<1 mIU/ml). CONCLUSIONS: This study shows the excellent efficacy of the HBV vaccination program in Saudi Arabia 18 years after its launch. Based on this study and others, a booster dose for the adult population appears to be unnecessary.