Introduction: Illicit stimulants are often combined with alcohol in nightlife entertainment districts, an environment where aggressive behaviour commonly occurs. While alcohol and methamphetamine use are each associated with aggressive behaviour, relatively little is known about the impact of the combined use of alcohol and amphetamine-type stimulants (i.e., ecstasy [MDMA] and methamphetamine) on aggression. Method: Analysis of longitudinal data from a population-based sample of Australian young adult amphetaminetype stimulant users (n = 248) to examine: (a) prevalence and timing of simultaneous alcohol and amphetamine-type stimulant use and (b) predictors of ecstasy- and methamphetamine-related aggression and hostility. Prediction models of ecstasy- and methamphetamine-related aggression and hostility were developed using multivariate logistic regression. Results: Simultaneous alcohol consumption and amphetamine-type stimulant use was prevalent, with drinking generally occurring before consuming amphetamine-type stimulants and while ‘high’. Methamphetamine-related aggression and hostility was significantly associated with recurrent risky simultaneous methamphetamine and alcohol use (Adjusted Odds Ratio [AOR] 2.74, 95% CI 1.09–6.89), a high frequency and increasing use methamphetamine trajectory (AOR 7.23, 95% CI 1.27–41.03), and high trait aggression (AOR 5.78, 95% CI 2.53–13.20). In contrast, only trait aggression (moderate: AOR 3.01, 95% CI 1.55–5.84; high: AOR 5.02, 95% CI 2.38–10.61) was associated with ecstasy-related aggression and hostility. Conclusions: These findings indicate a link between risky patterns of simultaneous alcohol and methamphetamine use and methamphetamine-related aggression and hostility, independent of separate use of alcohol, methamphetamine and cannabis, trait aggression, psychosis, and gender. The policy challenges of amphetamine-type stimulant and alcohol use require a targeted, multidisciplinary approach.