From March to July of 2011, the authors investigated the prospective association between illicit drug use and cognitive functioning during the midadult years. A total of 8,992 participants who were surveyed at 42 years of age in the National Child Development Study (1999-2000) were included. The authors analyzed data on 3 cognitive functioning measures (memory index, executive functioning index, and overall cognitive index) when the participants were 50 years of age (2008-2009). Illicit drug use at 42 years of age was based on self-reported current or past use of any of 12 illicit drugs. Multivariable regression analyses were performed to estimate the association between different illicit drug use measures at 42 years of age and cognitive functioning at 50 years of age. A positive association was observed between ever (past or current) illicit drug use and cognitive functioning (beta = 0.62, P <0.001), although the effect size was small. Even though there was no clear evidence against the null hypothesis, drug dependence (beta = -0.27, P = 0.58) and long-term illicit drug use (beta = -0.04, P = 0.87) tended to be negatively associated with cognitive functioning. At the population level, it does not appear that current illicit drug use is associated with impaired cognitive functioning in early middle age. However, the authors cannot exclude the possibility that some individuals and groups, such as those with heavier or more prolonged use, could be harmed.