Background: Patients with schizophrenia have shown cognitive improvements following cognitive remediation, but the neuroplastic changes that support these processes are not fully understood. Aims: To use a triple-blind, placebo-controlled trial to examine neural activation before and after cognitive remediation or a computer skills training (CST) placebo (trial registration: NCT00995553)). Method: Twenty-seven participants underwent functional magnetic resonance imaging before and after being randomised to either cognitive remediation intervention or CST. Participants completed two variants of the N-back task during scanning and were assessed on measures of cognition, functional capacity, community functioning and symptoms. Results: We observed a group6time interaction in the left prefrontal cortex, wherein the cognitive remediation group showed increased activation. These changes correlated with improved task accuracy within the cognitive remediation group, whereas there was no relationship between changes in activation in untrained cognitive measures. Significant changes were not observed in other hypothesised areas for the cognitive remediation group. Conclusions: We replicated the finding that cognitive remediation increases left lateral prefrontal activation during a working memory task in patients with schizophrenia, suggesting this may be an important neural target for these types of interventions.