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Opioid dependence has become a public health problem in several countries. A cohort study was used to assess first-time dispensed opioids, in 2012–2015, by drug type, doses, oral morphine equivalents, and diagnoses, in Sweden. First-time opioid users aged 18–64 years, previously cancer-free and opioid-naïve for at least 6.5 years, were studied. Time trends in opioid use in Sweden 2006–2021 were also studied. During the study, 617,568 patients were dispensed opioids for the first time. The crude proportion of first-time opioid users in the population was 2.7% in 2012 and 2.6% in 2015. The combination product of codeine and paracetamol was the most frequent dispensed opioid with 322,818 patients (52.3%), followed by tramadol (120,271, 19.6%) and oxycodone (104,418, 16.9%). From 2012 to 2015, tramadol as first dispensed opioid dropped from 26.5% to 13.7% and oxycodone increased from 10.0% to 24.4%. For the four most commonly dispensed opioids, the median initial dispensal ranged from 250 to 400 oral morphine equivalents. The most common indication was fracture of the lower leg during inpatient care and back pain for specialized outpatient care. Trends in dispensed opioids in Sweden show a shift from tramadol to oxycodone, but do not show an increase in total opioid use. [ABSTRACT FROM AUTHOR]