This study investigates changes in neurobiological characteristics after a cognitive skills program for prisoners. It was hypothesized that prisoners who completed a cognitive skills training program would show improved neurocognitive functioning and changes in heart rate (HR) activity. In addition, it was expected that neurobiological changes were related to behavioral improvement. Male adult prisoners were included in the study and divided into two groups: the "intervention group"—prisoners participating in a cognitive skills training program—and the "control group"—prisoners placed on a waitlist. Several neurocognitive skills and HR activity measures were assessed at pre- and posttest assessment. In addition, trainers, prison officers, and prisoners were requested to evaluate behavioral changes over time. Results did not confirm the hypotheses. The absence of both neurobiological and behavioral improvement is discussed in light of the measures used, the content and duration of the current intervention program, and the prison setting.