BACKGROUND: Understanding personality differences between injectors and non-injectors in substitution treatment may provide new insights to help improve treatment programs. OBJECTIVE: The aim of this study was to compare drug injectors and non-injectors in terms of personality disorders and dimensions. METHODS: Forty participants recruited from substance abuse treatment centers (23 injectors and 17 non-injectors) completed the self-report Personality Diagnostic Questionnaire 4th version and Temperament and Character Inventory. Mann-Whitney U tests were used to compare means of personality disorder traits, temperament, and character differences between injectors and non-injectors. RESULTS: The mean (SD) age of the sample (72.5% male) was 36.5 (8.7) years. Injectors reported more borderline personality disorders and increased global personality disturbance (p < .05). Similarly, Anticipatory worry, Shyness, and Fatigability facet scores were higher among injectors (p < .01). Attachment, Purposeful, and Congruent second nature facet scores were higher among non-injectors (p < .01). CONCLUSION: According to the route of drug administration, drug dependents differed in terms of personality disorders and dimensions. SCIENTIFIC SIGNIFICANCE: These results may have implications for the implementation of treatment programs. New research in this area may contribute to the understanding and prevention of intravenous drug use.