The purpose of this study was to investigate the relationship between sex, hopelessness levels and substance dependence levels alongside other associated variables among substance users in Ireland. The study consisted of a cross-sectional, psychometric and between-subjects design. Participants included 16 clients attending a six-month rehabilitative program at Coolmine Therapeutic Community, and 54 non-clinical substance users from the general public in Ireland. A purpose-designed questionnaire, The Leeds Dependence Questionnaire (LDQ), The Beck Hopelessness Scale (BHS), Perceived Stress Scale, BriefCope Scale were used. Hopelessness, gender, previous treatment, family dependence history, stress levels, and coping styles are the predictor variables. Substance dependency level is the criterion variable. A multiple regression analysis indicated the combination of the 23 predictor variables has a significant predictive value in relation to substance user's levels of dependence (Adjusted R Square = 0.686, F(23,46) = 7.558, p>0.05).