Introduction. Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders. Although lisdexamfetamine dimesylate (LDX) offers a treatment alternative, clinical evidence of LDX for ADHD has not been explored in Latin American pediatric population. Objective. To evaluate the LDX response in Mexican pediatric patients with ADHD. Method. We designed a quasi-experimental, uncontrolled before and after study to evaluate the LDX response in patients with severe ADHD. We established a diagnosis of ADHD according to DSM-5 criteria. We formed three groups: without previous treatment (group A), in treatment with stimulant drugs (group B) or in treatment with non-stimulant drugs (group C). Prior to the start of the study, letters of consent and informed consent were signed. We evaluated the effect of LDX based on the difference between ADHD-RS scores at the beginning and after six months. Results. We recruited a total of 144 patients (group A: 48 patients, group B: 57 patients, group C: 39 patients). All the groups showed a significant decrease in the mean score of ADHD-RS (Attention Deficit Hyperactivity Disorder Rating Scale) at six months (group A 37.57 vs. 22.34, p