Background To provide insight into the longitudinal dynamics of opioid use throughout the overdose crisis, this study estimated the separate influences of age, period and cohort on prescription opioid use during 1999–2018 in the USA.

Methods Data from 10 cycles of the cross-sectional National Health and Nutrition Examination Survey were used to conduct an age–period–cohort analysis of the prevalence of prescription opioid use (n=63 500 across 1999–2018). Temporal trends were graphically visualised. The median polish approach was used to estimate age, period and cohort-related effects on prescription opioid use.

Results Prescription opioid use broadly increased across the lifespan, with steeper prevalence increases observed from young adulthood to mid-adulthood. Period-related variation was consistent with recognised nationwide declines in opioid prescribing. While there was no evidence of systematic cohort effects, compared with individuals born in 1951–1954, those born during 1963–1966 had greater prescription opioid use (prevalence ratio (PR)=1.23, 95% CI: 1.05 to 1.43), whereas the 1991–1994 and 1999–2002 cohorts had lower prescription opioid use (PR_91-94=0.70, 95% CI: 0.50 to 0.98; PR_99-02=0.72, 95% CI: 0.63 to 0.81).

Conclusion In the USA, longitudinal trends in prescription opioid use during 1999–2018 were predominantly driven by age and period influences. The cohort of youngest baby boomers experienced greater prescription opioid use, whereas recent-born cohorts have had lower use. As the overdose crisis continues evolving, such population-level characterisations of age, period and cohort dynamics are instrumental in understanding opioid use and can inform prevention and intervention approaches by identifying population groups more likely to use opioids who, thus, may also experience related outcomes.