ABSTRACT Objective: To compare the consequences of psychoactive substance use among users of mental health services in Brazil and Portugal. Method: Cross-sectional, comparative, quantitative study, carried out with 362 users of two specialized treatment services in the cities of São Paulo (n = 200) and Lisbon (n = 162). Data collected in 2019 through the application of the Substance Addiction Consequences scale. A descriptive analysis and ordinary least squares and logistic regressions were performed. Results: All dimensions assessed by the scale were more severe for Brazilian users, with a difference for the physical domain and cognitive skills (p < 0.01). Brazilian participants were more likely to consume cocaine (p < 0.01) and have psychosis (p = 0.02) and Portuguese participants to have hepatitis (p < 0.01), personality disorders (p < 0.01), use benzodiazepines (p < 0.01) and tobacco (p < 0.01), and receive pharmacological support (p < 0.01). Conclusion: It was found that Brazilian users have more serious consequences related to substance use, and Portuguese users have more comorbidities and exposure to risky consumption. It emerges that Portuguese responses minimize the consequences severity.