Introduction Studies have shown higher rates of psychopathology and cognitive difficulties among relatives of schizophrenia patients than among the general population. This study aimed to analyze the relationship between clinical and neuropsychological characteristics in children and adolescents at high genetic risk for schizophrenia. Methods Participants were 26 children and adolescent first-degree relatives of subjects diagnosed with schizophrenia (high-risk [HR] group) and 20 controls whose parents and siblings did not meet DSM-IV criteria for any psychotic disorder. These two groups were matched by age, sex and socio-economic status and clinical and neuropsychological assessments were completed by all participants. Results Among HR children 42.3% were diagnosed with one or more DSM-IV axis I psychiatric disorders. The most common diagnoses were attention deficit/hyperactivity disorder (ADHD) (34.6%) and generalized anxiety disorder (3.8%) There were significant differences between HR children and controls with respect to prodromal symptoms, behavioral problems and premorbid adjustment, as well as on the majority of intelligence subscales, working memory and logical memory. When differences between HR with ADD (HR-ADD), HR without ADD (HR-NADD) and controls were analyzed, significantly higher scores on clinical scales of prodromal symptoms, behavioral problems and premorbid adjustment were found in HR-ADD than in HR-NADD or controls. There were no significant differences in cognitive domains between HR-ADD and HR-NADD, but there were between HR-ADD and controls and between HR-NADD and controls on the Verbal Comprehension Index, Perceptual Reasoning Index, Working Memory Index and GAI. Conclusions Compared to controls, HR children showed more clinical symptoms and cognitive abnormalities. HR children with ADD had worse clinical symptoms than did HR without ADD, although there were no differences in terms of cognitive abnormalities. Both HR groups seem to have similar deficits in neuropsychological performance.