Alcohol is related to HIV risk behaviors in southern Africa and these behaviors are correlated with sensation seeking personality and alcohol outcome expectancies. Here we report for the first time the associations among sensation seeking, substance use, and sexual risks in a prospective study in Africa. Sexually transmitted infection clinic patients in Cape Town South Africa (157 men and 64 women) completed (a) baseline measures of sensation seeking, sexual enhancement alcohol outcome expectancies, alcohol use in sexual contexts, and unprotected sexual behaviors and (b) 6-month follow-up measures of alcohol use in sexual contexts and unprotected sexual acts. Results confirmed that sensation seeking predicts HIV risk behavior and sensation seeking is related to alcohol outcome expectancies which in turn predict alcohol use in sexual contexts. HIV prevention counseling that addresses drinking in relation to sex is urgently needed in southern Africa.