Why certain individuals progress to severe dengue disease is unknown. In this study, blood groups associated with dengue disease were investigated. ABO phenotypes were identified by use of serum from 399 patients with dengue-virus infection who participated in a cohort study. ABO blood-group frequencies were similar in primary versus secondary dengue-virus infections. However, in secondary infection, individuals with blood group AB were likely to have dengue hemorrhagic fever grade 3 than either grades 1 and 2 combined (corrected P value, <.0001; odds ratio, 0.097 [95% confidence interval, 0.03-0.33]) or dengue fever (corrected P value, <.0001; odds ratio, 0.119 [95% confidence interval, 0.04-0.37]). To our knowledge, this is the first report demonstrating an association between ABO blood group and the severity of dengue disease.