People with borderline personality disorder (BPD) commonly have co-occurring mental health conditions that may be accounted for by higher-order factors in dimensional models of psychopathology. BPD Compass is a cognitive-behavioral treatment developed to target broad personality domains (i.e., negative affectivity, antagonism, disinhibition) associated with BPD and related conditions. The purpose of the present study was to explore the extent to which BPD Compass can serve as a transdiagnostic intervention for these comorbid conditions. Participants (N = 100; Mage = 28.13, 73.7% female, 79.6% White, 66% sexual minority) were assigned to either immediately begin treatment (randomized and naturalistic) or receive treatment after an 18-week waiting period. At baseline, participants met criteria for an average of 3.28 (SD = 2.02, range: 0-8) comorbid diagnoses ranging in clinical severity from 3.30 (for substance use disorder) to 4.91 (for persistent depressive disorder). Post-treatment clinical severity ratings (CSRs) for those randomized to receive BPD Compass were below clinical thresholds for all assessed conditions except premenstrual dysphoric disorder, whereas post-waitlist CSRs remained above clinical thresholds for all disorders except bipolar II, agoraphobia, and major depressive disorder. Collapsed across all patients who received BPD Compass, pre- to post-treatment improvements in were significant and large in magnitude for most disorders assessed. These results suggest that BPD Compass may be an efficacious transdiagnostic intervention, though our small sample and high rate of dropout warrant further study.