The research aimed to explore the salience of different motives for substance use among alcohol, tobacco and marijuana users, and to investigate the difference in motives' salience with regard to frequency of substance use and respondents' socio-demographic characteristics. Data were collected among subsamples of alcohol, tobacco and marijuana users drawn from the representative sample of Croatian citizens (N = 4756). Respondents assessed four types, and for marijuana use five types of motives for each substance use (enhancement, social, conformity, coping, and expansion). The enhancement motives were assessed as the most, and conformity motives as the least salient motives among all groups of substance users. Generally, enhanced salience of motives was related to the frequency of all types of substance use. While age had significant effect on the salience of social motives for tobacco use, gender and marital status had significant effect on the salience of all motives for alcohol use, and age had significant effect only on the salience of enhancement and social motives for alcohol use. Among marijuana users, only marital status had significant effect on the salience of expansion motives for marijuana use. Results are discussed within the framework of motivational models for substance use.