Anxiety sensitivity (AS) is a well-established transdiagnostic risk factor for anxiety and mood psychopathology including suicide. A variety of interventions using cognitive-behavioral skills as well as cognitive bias modification (CBM) suggest that AS can be quickly and effectively reduced in nonclinical and nontreatment seeking samples. However, it is unclear whether AS reduction protocols will have efficacy for more severe clinical samples. Moreover, the combination of cognitive-behavioral techniques with CBM focused on changing interpretation bias (CBM-I) related to AS has not been evaluated. A patient sample with co-occurring anxiety psychopathology and active suicidal ideation (N = 74) was randomly assigned to a brief 1-session computerized treatment including: (a) psychoeducation and interoceptive exposure (i.e., cognitive anxiety sensitivity treatment [CAST]) plus CBM-I for AS; or (b) health information condition plus sham CBM for AS. Participants were assessed immediately after the 1-hr intervention as well as at 1- and 4-month follow-ups. Consistent with hypotheses, participants in the active treatment showed significantly greater AS reduction that was maintained through follow-up (effect sizes ranged from medium to large for the overall AS and the AS subscales). Mediation analyses suggested that changes in AS mediated suicide outcomes. In sum, these are the first findings to suggest that brief AS reduction protocols have efficacy both in terms of risk and symptom outcomes in patient samples showing active suicidal ideation. (PsycINFO Database Record