Adolescents in sub-Saharan Africa and in Botswana in particular continue to bear the brunt of the HIV epidemic. This analysis assessed gender differences among theory-based sexual and reproductive health protective and risk factors in a cross-sectional sample of 228 Batswana adolescents. Incongruence between preferred and actual sources of sexual information and several important gender differences in parent-adolescent relationships, psychosocial influences, and adolescent sexual behaviors were identified. Parents were the fourth most common source of information about sex; yet, over three-quarters of adolescents preferred to have parents teach them about sex. Boys reported more positive relationships with their parents and girls reported more positive attitudes toward transactional sex. Both boys and girls reported similarly low levels of parental monitoring, parental communication, and parental responsiveness, all of which are important protective factors. These findings suggest interventions should address these gender differences and consider offering parallel interventions for adolescents and their parents in Botswana.