Background and aims: Alcohol and other drug use is common in early adulthood; however, research on contemporary polysubstance use patterns—defined as use of multiple psychoactive substances—and their associated factors is limited. This study aimed to identify groups with differing polysubstance use patterns and to examine associations with individual, family and socio-environmental factors.

Design: This is a cohort study based on data from the Growing Up in Ireland (GUI) study. GUI employed a two-stage clustered sampling design, using the national primary school system as the initial sampling frame. Sampling was stratified by county, sex, disadvantaged status, religious denomination and total number of nine-year-old pupils.

Setting: GUI is a nationally representative cohort of young people in the Republic of Ireland.

Participants: This study includes 4695 participants (49.5% female) who completed all four waves of GUI. Wave 1 took place in 2007/2008 when participants were aged nine, followed by wave 2 at age 13 in 2011/2012, wave 3 at age 17/18 in 2015/2016 and wave 4 at age 20 in 2018/2019.

Measurements: We used eight indicators of substance use at age 20: Alcohol Use Disorders Identification Test (AUDIT) scores, e-cigarette, tobacco, cannabis, cocaine, ecstasy, ketamine and other drug use in a latent class analysis, and examined associations with age, sex, age at first alcohol, emotional and behavioural difficulties, socioeconomic status, household structure, non-parental address, region, familial, peer and neighbourhood substance use using survey-weighted multinomial regression.

Findings: Four latent classes were identified: limited use (33.8%), alcohol, tobacco and cannabis use (43.0%), polysubstance use (16.2%) and heavy polysubstance use (7.0%). Both polysubstance classes, which together accounted for 23.2% of the cohort, had elevated probabilities of using five or more substances, including risky alcohol use, tobacco, cannabis, cocaine and ecstasy, with individual substance use probabilities (P) ranging from 0.63 to 0.99. The heavy polysubstance class was characterised by more frequent and diverse substance use, notably including ketamine (P = 0.90). Male sex [adjusted odds ratio (aOR) 2.7, 95% confidence interval (CI) = 1.7–4.2], familial (aOR 3.8, 95% CI = 1.9–7.6) and peer substance use (aOR 13.5, 95% CI = 6.3–29.2), a non-parental address (aOR 2.3, 95% CI = 1.4–3.8) and living in the Dublin region (aOR 1.9, 95% CI = 1.1–3.3) were associated with heavy polysubstance use, relative to the limited use class.

Conclusions: Nearly one in four 20-year-olds in Ireland appears to engage in polysubstance use, representing a significant public health concern. Polysubstance use among 20-year-olds in Ireland appears to be associated with being male, having family members and peers who use substances, not living with parents and living in or near Dublin.