This pilot study examines personality characteristics using the Five Factor Model combined with measures of Sensation Seeking and religious/spiritual well-being in two Austrian samples of substance abusers. Sixty-three male addicts (33 polydrug dependents, 30 alcohol dependents) treated in a therapeutic community setting were tested with the Neo Personality Inventory Revised Version, the Sensation Seeking Scale, and the Multidimensional Inventory for Religious/Spiritual Well-Being. Results show significant personality differences between alcohol and polydrug abusers. Whereas higher levels of Neuroticism and lower levels of Openness to experience were found in both substance dependents groups, low levels of Conscientiousness and low levels of Agreeableness were merely shown in polydrug abusers. Furthermore, they exhibit less religious/spiritual well-being and high Sensation Seeking. Thus, the results seem to highlight a link between polydrug dependence and problematic personality structure. Findings have implications for understanding differences between various substance abusers and for novel treatment opportunities in the therapeutic community setting.