Objectives: Despite medical evidence that female-to-male oral sex (fellatio) carries a lower risk for HIV transmission than unprotected vaginal intercourse, little research exists on the practice of fellatio in Africa. The objective of this study was to document the prevalence of oral sex in Malawi, and to provide the first evidence on factors associated with the practice in sub-Saharan Africa. Methods: We used two samples of men from Malawi—one rural and one urban—to examine the prevalence of oral sex, as well as factors that were associated with the knowledge and practice of oral sex. Results: While 97% of the rural sample and 87% of the urban sample reported having had vaginal sex, just 2% and 12%, respectively, said they had ever received oral sex. Only half of the rural sample, and less than three quarters of the urban sample, reported having heard of oral sex. Education, exposure to newspapers and television, and condom use significantly predicted oral sex knowledge after controlling for other confounding factors, while exposure to radio did not. Conclusions: The large gap between sexual activity and oral sex prevalence suggests that fellatio should be taken into consideration as a potential component of an HIV prevention strategy, but further quantitative and qualitative research that includes women as well as men is needed to understand potential benefits and drawbacks.