Objectives: We evaluate the extent to which subjective and objective measures of economic distress account for differences in substance abuse between the mid-1990s and early-2010s. Methods: We use cross-sectional survey data for national samples of Americans aged 25-74 in 1995-96 (N = 3034) and 2011-14 (N = 2598). Using a logit model, we regress dichotomous indicators of drug and alcohol abuse on economic distress. Results: After adjusting for sociodemographic characteristics, the odds of drug abuse in the early-2010s among older individuals (aged 50+) were 2.9 times (95%CI 1.9-4.2) those of the mid-1990s, but there was no statistically significant period difference in drug abuse among younger individuals. Measures of model performance demonstrate that subjective measures of economic distress are better predictors of drug abuse than objective measures. The subjective measures also account for a larger share (26%) of the increase in drug abuse at ages 50+ than the objective measures (6%). We cannot draw clear conclusions regarding alcohol abuse because results are sensitive to specification. Conclusions: The rise in drug abuse among midlife Americans may relate to perceived economic distress that is not captured by standard economic measures.