We use single equation and system instrumental variable models to explore if individuals smoke during times of stress (the motivation effect) and if they are successful in self-medicating short-term stress (the self-medication effect). Short-term stress is a powerful motivator of smoking, and the decision to smoke could trigger biological feedback that immediately reduces short-term stress. We use data on self-reported smoking and stress from 240,388 current and former smokers. We instrument short-term stress with temporal distance from September 11, 2001 (using date of interview). We instrument smoking with cigarette accessibility measures of cigarette price changes and distance to state borders. In the absence of accounting for endogeneity, we find that smoking is associated with increases in short-term stress. However, when we account for endogeneity we find no evidence of smoking affecting short-term stress. We do find a consistent positive effect of short-term stress on smoking.