Background: Driving under the influence of multiple substances is a public health concern, but there is little epidemiological data about their combined use and putative impact on driving in low and middle-income countries where traffic crashes have been clustering in recent years. The aim of this study is to estimate the prevalence of alcohol and drug use – as well as their associated factors – among drivers in the context of alcohol outlets (AOs). Methods: A probability three-stage sample survey was conducted in Porto Alegre, Brazil. Individuals who were leaving AO were screened, with the selection of 683 drivers who met the inclusion criteria. Drivers answered a structured interview, were breathalyzed, and had their saliva collected for drug screening. Prevalences were assessed using domain estimation and logistic regression models assessed covariates associated with substance use. Findings: Benzodiazepines 3.9% (SE 2.13) and cocaine 3.8% (SE 1.3) were the most frequently detected drugs in saliva. Among drivers who were going to drive, 11% had at least one drug identified by the saliva drug screening, 0.4% two, and 0.1% three drugs in addition to alcohol. In multivariable analyses, having a blood alcohol concentration (BAC) > 0.06% was found to be associated with a 3.64 times (CI 95% 1.79–7.39) higher chance of drug detection, compared with interviewees with lower BACs.