Research has shown that measures of reactivity to distress—including distress tolerance and physiological reactivity to stress—are dysregulated in women who misuse alcohol. These variables may interact and create a risk profile for young adult women, reflecting patterns of stress reactivity that confer a risk for alcohol misuse. The current study tested this hypothesis by examining the independent and interactive associations of subjective distress tolerance, behavioral distress tolerance, and physiological stress reactivity with women’s alcohol misuse. The study was conducted with a sample of 91 college women recruited on a large northeastern university campus. Results showed that subjective levels of distress tolerance and physiological reactivity to stress (skin conductance reactivity, SCR), but not behavioral distress tolerance, were independently associated with alcohol misuse. In addition, subjective distress tolerance moderated the relationship between SCR and negative alcohol-related consequences. Specifically, women with low physiological reactivity (SCR) to a stressful task and greater urge to quickly rid themselves of distress (low subjective distress tolerance) endorsed a significantly greater number of adverse consequences from their alcohol use. These results extend prior findings by showing that, even among a nonclinical sample of women, lower stress reactivity in combination with low subjective distress tolerance is associated with increased risk for various drinking-related negative consequences.