This study was designed to assess the ability of the Minnesota Multiphasic Personality Inventory (MMPI-2) MacAndrew Alcoholism Scale (MAC-R) to differentiate between outpatients with personality disorders with Substance-Related Disorders (SRDs) and without SRDs. MMPI-2 validity, clinical, and MAC-R scale scores were compared in an SRD Cluster B group (comprised of Narcissistic, Antisocial, Borderline, and Histrionic; n = 15), a non-SRD Cluster B group (n = 33), and a non-SRD group with personality disorders from Clusters A and C (n = 18). Results revealed that the substance-abusing Cluster B group scored significantly higher on the MAC-R ( p < .0001) as well as the Psychopathic Deviate scale ( p < .01). Dimensional analyses illustrated that MAC-R scores were related to the presence of an SRD diagnosis (rpb = .70, p < .0001) and diagnostic criteria for Antisocial Personality Disorder (r = .60, p < .0001). Stepwise regression revealed that (in order of magnitude) the presence of a substance-abuse diagnosis followed by diagnostic criteria for Antisocial and Histrionic Personality Disorders were most related to MAC-R scores (R = .78, R2 = .60). This indicates that the MAC-R may be more related to the presence of an SRD than has been suggested, and when used in outpatient settings as MacAndrew (1965) intended, the MAC-R may be useful as a screening device for assessing SRD among outpatients with Axis II psychopathology. © 2001 John Wiley & Sons, Inc. J Clin Psychol 57: 801–813, 2001.