A fundamental public health strategy to reduce the risk of HIV/AIDS is to increase levels of awareness and knowledge about the disease. Although knowledge about HIV/AIDS and protective sexual behaviour are linked theoretically, relatively little is known about their empirical relationship. Using Demographic and Health Survey data from 23 low- and middle-income countries, this study used multilevel logistic regression models: to examine cross-national variability in the relationship between HIV/AIDS knowledge and protective behaviour (condom use and restricted sex); to investigate the moderating influences of women’s educational attainment on this relationship; and to test the extent to which severity of the HIV/AIDS epidemic accounts for cross-national variability in the association between HIV/AIDS knowledge and protective behaviour. There was an association between increased knowledge of HIV/AIDS and condom use that varied in strength and form cross-nationally. This cross-national variation was accounted for partially by the socioeconomic characteristics of women resident in the study countries and between-country differences in the severity of the HIV epidemic. While education modified the association between HIV/AIDS knowledge and protective behaviour – stronger associations at lower levels of education – epidemic severity exerted a stronger influence on behaviour than any other characteristic. Finally, this study indicates that protective sexual practices are disturbingly low. In eight of 23 countries, overall levels of condom use to prevent STDs and HIV/AIDS were less than 5·0%. Waiting for the spread of HIV/AIDS infection to change sexual practices in low- and middle-income countries will result in dramatic unnecessary suffering.