<b>Background</b> : Non-medical use of prescription drugs (NMUPD) is an increasing phenomenon associated with physical and psychological consequences. This study investigated the effects of distinct forms of stress on NMUPD. <b>Methods</b> : Data from 5308 young adult men from the Swiss cohort study on substance use risk factors (C-SURF) were analysed regarding NMUPD of sleeping pills, tranquilizers, opioid analgesics, psychostimulants, and antidepressants. Various forms of stress (discrete, potentially traumatic events, recent and long-lasting social-environmental stressors) during the period preceding the NMUPD assessment were measured. Backward log-binomial regression was performed and risk ratios (RR) were calculated. <b>Results</b> : NMUPD was significantly associated with the cumulative number of potentially traumatic events (e.g. for opioid analgesics, RR = 1.92, <i>p</i>  < .001), with problems within the family (e.g. for sleeping pills, RR = 2.45, <i>p</i>  < .001), and the peer group (e.g. for tranquilizer use, RR = 2.34, <i>p</i>  < .01). Factors describing family functioning in childhood showed very few significant associations. Sexual assault by acquaintances was associated only with use of sleeping pills (RR = 2.91, <i>p</i>  p <.01); physical assault by acquaintances was not associated with NMUPD. Physical (e.g. for psychostimulants, RR = 2.01, <i>p</i>  < .001) or sexual assaults (e.g. for antidepressants, RR = 4.64, <i>p</i>  < .001) perpetrated outside the family context did show associations with several drug categories. <b>Conclusion</b> : NMUPD appears to be more consistently associated with discrete and potentially traumatic events and with recent social-environmental stressors than with long-lasting stressors due to family functioning during childhood and youth. Physical and sexual assaults perpetrated by strangers showed more associations with NMUPD than those perpetrated by a family member.