A self-report measure of the Five-Factor Model (FFM) of personality, NEO-PI-R, was administered to a sample of patients with borderline (BPD, N = 29) or avoidant PD (AVPD, N = 34), admitted to a day treatment program, to investigate the NEO-PI-R profiles of the disorders, and the ability of NEO-PI-R to discriminate between the two disorders. The diagnoses were assessed according to the LEAD standard. AVPD was associated with high levels of Neuroticism and Agreeableness, and low levels of Extraversion and Conscientiousness. BPD was associated with high levels of Neuroticism and low levels of Agreeableness, Extraversion, and Conscientiousness. Eighty-eight percent of the AVPD group had high scores on Neuroticism and low scores on Extraversion, whereas 65% of the BPD group were high on Neuroticism and low on Agreeableness. The Extraversion and Agreeableness scales of NEO-PI-R discriminated between patients with BPD and those with AVPD. Patients with BPD scored significantly higher on the Angry Hostility and Impulsiveness subscales of Neuroticism and significantly lower on three Extraversion subscales, three Agreeableness subscales, and one Conscientiousness subscale. At the DSM-IV criterion level, there were more significant relationships between the subscales of NEO-PI-R and the AVPD criteria than with the BPD criteria. The findings suggest that the FFM has good discriminating ability regarding BPD and AVPD. However, there may be a closer conceptual relationship between the FFM and AVPD than between the FFM and BPD.