Casual heterosexual sex remains a significant contributor to HIV transmissions in Ghana. The study used data from the 2008 Ghana Demographic and Health Survey (GDHS) to assess the socio-demographic, economic and spatial factors influencing unprotected casual heterosexual sex among men and women. The results of the binary logistic regression models revealed that women aged 35-44 had significantly higher odds of engaging in unprotected casual heterosexual sex than those aged 15-24, unlike the men. There were significantly lower odds of unprotected casual heterosexual sex for women and men with exposure to print media compared with those without exposure. Compared with men residing in the Western Region, unprotected casual heterosexual sex was significantly less likely among those in the Upper East Region. There is the need for behavioural change campaigns in Ghana that take into consideration the multiplicity of factors that determine unprotected casual heterosexual sex.