Background. The compounded effects of the decline of low-skilled labor and the Great Recession of 2008 has caused the employment prospect of poorly educated workers to deteriorate, which may have led to substance misuse as a coping mechanism. Objective. This study aims to determine whether poor employment prospect has a positive association with the likelihood of having a substance use disorder (SUD) among middle-aged males in the United States. Methods. Using data from the 2008 to 2014 National Survey on Drug Use and Health, estimated linear probability models were utilized to evaluate the relationship between poor employment prospect and SUD status, potential moderators in the relationship, and a potential mediator – mental distress – in the relationship. In our secondary analysis, two separate linear probability models were compared to determine whether the relationship between poor employment prospect and SUD status differed across the recent economic cycle and to see how much of the relationship is accounted for by mental health. Results. The analysis indicated a positive correlation between poor employment prospect and SUD status, which is mediated by psychological distress. The results from the secondary analysis found that the relationship between poor employment prospect and SUD status is most magnified during times of macroeconomic upheaval and confirms that mental health explains a significant amount of the relationship. Conclusion. Having poor employment prospect is associated with an increased likelihood of having a SUD among middle-aged men. The relationship is strongly accounted for by psychological distress.