AIMS:To investigate childhood influences on onset of injection drug use. DESIGN:Matched case-control study. SETTING:Edinburgh, Scotland. PARTICIPANTS:A total of 432 individuals presenting at a community health facility with injection drug use and 432 age- and sex-matched non-injecting controls recruited through the same facility. MEASUREMENTS:Main exposures considered were family structure and experience of public care, carer substance use, physical and sexual victimization and conduct problems, all measured at personal interview. The outcome was history of adult injection drug use recorded in medical records corroborated at personal interview. FINDINGS:Compared to two-parent families all other family structures were associated with increased risk of injection drug use, the greatest increased risk being associated with public care. Violence, criminality and financial problems in the family were also associated with increased risk, as were all types of carer substance use. The greatest increased risk was associated with markers of early conduct problems, particularly school exclusion and childhood contact with the criminal justice system. In multivariable analyses the strongest risk factors for later injecting were always having lived with a relative or family friend (not always a parent) and in care/adopted/foster home at any point [odds ratio (OR) = 2.66, 95% confidence interval (CI): 1.02-6.92 and OR = 2.17, 95% CI: 0.91-5.17, respectively], experienced violence from parent or carer (OR = 2.06, 95% CI: 1.26, 3.38) and early evidence of conduct problems [ever excluded from school (OR = 2.73, 95% CI: 1.68, 4.45); childhood criminality (ever arrested by police pre-adult OR = 3.05, 95% CI: 1.90, 4.89, ever been in borstal/young offenders/list D school OR = 4.70, 95% CI: 2.02, 10.94)]. After adjustment for family structure and conduct problems, sexual victimization was associated weakly with injecting onset (OR = 1.29, 95% CI: 0.76-2.19). More than 70% of injection drug use onset appeared attributable to the risk factors identified. CONCLUSIONS:Injection drug use in adults is associated strongly with prior childhood adversity, in particular not living with both parents and early conduct problems. Prevention initiatives should also consider these risk factors.