This study aims to investigate the relationship between social support and non-safe use of nicotine and alcohol among medical students, in relation to other contributing factors. Data were collected during 2002-2003. Participants (N = 135), medical students at the Democritus University of Thrace, Alexandroupolis, Greece, were allocated into groups per sex according to their smoking and alcohol drinking patterns. Comparisons were made with respect to rating scores on measures assessing perceived social support, psychopathological problems, stressful life events, physical health, and satisfaction with life. Data were analyzed using chi-square, Mann-Whitney U test, and factor analysis. Female students' non-safe use of licit substances is positively related to higher scores on perceived social support and lower scores on psychopathological dimensions. Despite some limitations of this study, findings bring about implications on antismoking and antialcoholic campaigns.