To add to the open question whether cognitive impairments predict clinical outcome in schizophrenia, a sample of 125 first episode patients was assessed at the onset and over one year of controlled long-term treatment within a study of the German Research Network on Schizophrenia. No relapse according to predefined criteria occurred within the first year, but a total of 29 patients fulfilled post-hoc criteria of "clinical deterioration". Impairments in cognitive functioning assessed by the Trail-Making Test B at the onset of long-term treatment differentiated between patients with vs. without later clinical deterioration and proved to be a significant predictor of the clinical course in a regression analysis outperforming initial clinical status as predictor. However, low sensitivity (72%) and specificity (51%) limit possibilities of a transfer to individual predictions. As a linear combination of neuropsychological and psychopathological variables obtained highest predictive validity, such a combination may improve the prediction of the course of schizophrenic disorders and may ultimately lead to a more efficient and comprehensive treatment planning.