This study examined the relationship between the personality profile of a sample of cocaine users and the presence of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnoses and the severity of substance use. A total of 120 participants (46 women, mean age: 23.8 years) from nonclinical settings in Barcelona, Spain, 2003-2006, were assessed using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) and the Temperament and Character Inventory-Revised version (TCI-R). Most of the participants had completed more than primary education, nearly half of them were employed, one third lived with parents, and near a quarter had some criminal record. Snorting was the main route of cocaine administration. They were using a mean of 1.82 substances. Cocaine users with low Self-Directedness, low Cooperativeness, and high Self-Transcendence scores in the TCI-R, with high severity of substance use and psychiatric comorbidity, would be suggestive of a possible specific phenotype. The limitations and implications of the study are discussed.