Decision-making is a complex process that is important for everyday life. This study examined the effect of the degree of success, and outcome uncertainty, on decision-making and associated neural substrate activation in schizophrenia subjects (SZS) and normal comparison subjects (NCS). A total of 15 subjects with a diagnosis of schizophrenia and 15 age- and education-matched NCS participated in this study. These subjects completed the two-choice prediction task during functional magnetic resonance imaging. Decision-making characteristics and activation of neural substrates were obtained at 20, 50, or 80% error rate. Success and uncertainty influenced the behavioral characteristics on the two-choice prediction task, and the task-related activation in SZS and NCS. Neither success nor uncertainty differentially affected the behavioral characteristics of SZS relative to NCS during the two-choice prediction task. Nonetheless, there was a significant interaction between group and error rate in bilateral parietal cortex. The activation in NCS was the highest when the outcome was most uncertain. In contrast, task-related activation in SZS was not modulated by the degree of uncertainty. Thus, SZS failed to utilize the parietal cortex to process decision-making situations with highly uncertain outcomes.