Background: Lowered neuropsychological performance is evident in youth with type 1 diabetes, although evidence for associations with specific illness variables is inconsistent. This study examined the neuropsychological profiles of a cohort of youth with type 1 diabetes studied prospectively from diagnosis 12 yr previously.Methods: A total of 106 youth with type 1 diabetes and 75 healthy controls participated. There were no significant group differences on Full-scale IQ assessed on study entry 12 yr previously, current socioeconomic status, gender distribution, or age. Neuropsychological tests assessed eight cognitive domains: verbal abilities, perceptual reasoning, new learning, working memory, non-verbal processing speed, mental efficiency, divided attention, and sustained attention. Episodes of serious hypoglycemia and HbA 1c levels were recorded from diagnosis.Results: Youth with type 1 diabetes performed more poorly than controls on working memory (p < .05). Early onset diabetes was related to poorer sustained (p < .001) and divided attention (p = .001), new learning, and mental efficiency (both p < .05). Hypoglycemia was found to adversely effect verbal abilities, working memory, and non-verbal processing speed (all p < .05). Poorer working memory was associated with hyperglycemia (p < .05). Youth with any combination of two or three illness risk factors (i.e., early onset diabetes, hypo-, hyperglycemia), performed more poorly than controls and youth with no or one risk on verbal abilities, working memory, and mental efficiency.Conclusions: This study documents poorer neuropsychological performance and its association with illness risk factors in youth with type 1 diabetes. Findings suggest that early disease onset and hypoglycemia impact on the developing central nervous system, with hyperglycemia playing a lesser role.