• MPH improved performance on neuropsychological subtests. • The presence of comorbidity affects the executive function of children with ADHD. • One of the largest studies to examine the effects of MPH on neurocognitive test scores. This study aimed to investigate the effects of methylphenidate (MPH) on scores on a neurocognitive test battery for individuals with various presentations of attention deficit/hyperactivity disorder (ADHD) and the effect of comorbidities on executive function. This study included 861 children and adolescents aged 7–17 years who were diagnosed with ADHD according to DSM-V criteria. The CNS Vital Signs Battery was utilized to compare the neuropsychological characteristics and MPH treatment responses of patients with predominantly inattentive (ADHD-I) and combined (ADHD-C) presentations of ADHD. Before MPH administration, a statistically significant difference was observed between groups only for complex attention. In addition, the overall prevalence rate of psychiatric comorbidities was 45.5%, and no statistically significant differences were found in the ADHD-I group pre- versus post-MPH administration. Prior to the administration of MPH, statistically significant differences were observed within the ADHD-C group between those with or without comorbidities. However, after MPH administration, these differences between the groups disappeared. The effects of MPH on improving scores on neuropsychological subtests were similar between the groups with different presentations of ADHD. Additionally, MPH treatment was effective despite the presence of comorbidities.