A growing proportion of the population is using opioids for longer time periods, but little is known about the characteristics of patients who are persistent opioid users. We therefore studied the association between socio-economic factors and persistent vs. short-term opioid use 4 years later. The background population is the complete Norwegian population in 2001. The study population is derived from two groups aged 35 years or older in 2001 who met one of the following criteria in 2005: (1) persistent opioid users (n = 15,113) or (2) short-term opioid users (n = 214,061). The applied definition of persistent opioid use corresponds to an average daily dose indicating likely daily use of opioids during 365 consecutive days. The socio-economic factors work status, income, marital status, immigrant status and education were obtained from the Population and Housing Census of 2001, and data on opioid use in 2005 were obtained from the complete national Norwegian Prescription Database. For logistic regression analyses, the study population was stratified by gender and by age over/under 67 years. In the 35- to 67-year-old age group, receiving a disability pension was more common in persistent opioid users compared with short-term opioid users (48% vs. 16% for women, 36% vs. 9% for men). Adjusted odds ratios for receiving a disability pension were 6.51 and 5.77 for women and men, respectively. Being divorced/separated was associated with being a persistent opioid user (odds ratio of 1.4 for both genders). There were also negative associations between persistent opioid use and attained education level, an unemployed working status and income status. Disability pension, not working, divorce, low income and low education in 2001 were associated with persistent opioid use in 2005.