Despite the growing theoretical and clinical interest in distress tolerance (DT) and its role(s) in psychopathology vulnerability, we lack knowledge regarding the: (1) nature and degree of associations between putatively related measures of DT, and (2) universal/differential nature of associations between these DT measures and psychopathological syndromes. Accordingly, the purpose of the current multimethod study was thus to investigate the relations between and among various self-report and behavioral DT measures, as well as to examine the measures' differential relations to multiple forms of mood and anxiety psychopathology and quality of life. Participants were 149 adults (61.3% women; M age = 23.4, SD = 8.8) who completed self-report [Distress Tolerance Scale (DTS;Simons & Gaher, 2005), Discomfort Intolerance Scale (DIS; Schmidt, Richey, & Fitzpatrick, 2006)] and behavioral (mirror-tracing, breath-holding, and CO 2 -enriched air tolerance tasks) measures of DT, as well as a structured clinical interview and quality of life measure. As hypothesized, the self-report DT measures were significantly related to one another and the behavioral DT measures were significantly related to one another, though the self-report and behavioral DT measures were orthogonal. Furthermore, DTS scores evidenced significant transdiagnostic relations to psychopathology and quality of life; lower levels of perceived tolerance of emotional distress were related to mood and anxiety disorder diagnostic status, greater levels of co/multi-morbidity, and poorer quality of life. In contrast, the behavioral DT measures were not related to any of the clinical outcomes studied. Implications of the present study for conceptualizing the nature of individual differences in DT construct(s), and the role(s) of these individual differences for psychopathology vulnerability, are discussed.