Introduction. This study aimed to estimate risks of cardiovascular and cerebrovascular events in patients treated with lisdexamfetamine dimesylate (LDX) compared with patients previously treated with other attention-deficit hyperactivity disorder (ADHD) medications (amphetamine, dexamphetamine, methylphenidate or atomoxetine). Methods. This population-based cohort study used data from Danish and Swedish medical and administrative national registers. The LDX cohort included adult patients initiating LDX with at least 12 months’ data preceding first LDX dispensing (index date). A random sample of patients treated with at least one non-LDX ADHD medication in the 6-24 months (but not less than 6 months) before index date (previous-users cohort) were matched to LDX users on age, sex, region and calendar year. The primary outcome, a composite of major adverse cardiovascular and cerebrovascular events (MACE), included first hospitalisation for acute myocardial infarction or stroke and out-of-hospital coronary heart disease or cerebrovascular disease death. Incidence rates (IRs) and IR ratios (IRRs) with 95% confidence intervals (CIs) of MACE were estimated using Poisson regression. Results. From Denmark vs Sweden, 5516 vs 40,163 LDX users and 27,494 vs 200,389 previous users were included. In Denmark, IRs of MACE per 1000 person-years (95% CI) were similar for LDX (1.63 [0.85-3.14]) and previous users (1.61 [1.28-2.01]). In Sweden, IRs (95% CI) were 1.40 (1.09-1.79) in LDX users and 1.17 (1.00-1.38) in previous users. Adjusted MACE IRRs (95% CI) for LDX versus previous use were 1.01 (0.48-2.13) in Denmark, 1.13 (0.75-1.71) in Sweden, and 1.10 (0.77-1.58) in the pooled analysis. Conclusion. Our findings suggest little to no increased risk of cardiovascular and cerebrovascular events in patients treated with LDX compared with patients previously treated with other ADHD medications.