This study examined, for the first time, the association between intoxication at last sexual intercourse and unprotected sex separately among HIV-positive and HIV-negative individuals. Data were derived from a nationally-representative survey of Uganda in 2011. Multivariable logistic regression analyses of the intoxication-unprotected sex association included adjustment for sociodemographic and behavioral covariates that were also examined as moderators of the association. Among HIV-positive individuals, intoxication was associated with unprotected sex, whereas among HIV-negative individuals, the intoxication-unprotected sex association was moderated by knowledge that condoms prevent HIV transmission. The odds of unprotected sex was 2.67 times greater among HIV-negative individuals who were unaware that condoms prevent HIV, an association not observed among those who possessed such knowledge. The results suggest that the intoxication-unprotected sex link be incorporated within Ugandan National HIV Prevention Strategies among HIV-positive and HIV-negative individuals. HIV-negative individuals who are unaware that condoms prevent HIV should be targeted for interventions focusing on increasing HIV transmission knowledge especially on the role of condoms in preventing the disease. The latter interventions should also identify those sociocultural and political beliefs about condom use that may serve as barriers to consistent condom use.