Psychoactive substance use has been typical of most traditional and modern societies and is maintained in the population despite the potential for abuse and related harms, raising the possibility that it (or its underlying causes) confers fitness benefits that offset its costs. Although it seems plausible that psychoactive substances have facilitated survival among ancestral and modern humans, it is not clear that this enhancement has translated into Darwinian fitness through mating and ultimately reproductive success. In the current study, we discuss potential mechanisms by which substance use might make unique contributions to mating success, attend to the possibility that the effects between substance use and mating success are instead confounded, and use structural equations and nationally representative data to determine whether these effects are more likely causal or spurious. Our findings indicate that once we know participants' scores on "third" variables at each round in early young adulthood, their substance use gives us little additional information about their current prospects for acquiring sexual partners and no additional information about of their future prospects. Thus, if adaptations for substance use evolved, their adaptive value does not seem to be found in mating success.