Objective The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Project produced a battery of tests, the MATRICS Consensus Cognitive Battery (MCCB), designed to assess cognitive treatment effects in clinical trials of patients with schizophrenia. In validation studies, the MCCB demonstrated excellent reliability, minimal practice effects and significant correlations with measures of functional capacity. This study addresses whether the MCCB demonstrates these favorable characteristics when administered in the context of the type of large multi-site industry trial for which it was designed. Methods In a clinical trial comparing risperidone and lurasidone, 323 clinically-stable outpatients with schizophrenia at 29 sites were assessed with MCCB at screening and a median of 15days later at baseline. A measure of functional capacity, the UCSD Performance-based Skills Assessment – Brief (UPSA-B) was administered at baseline. Results All 323 (100%) patients had sufficient data for computing a composite score according to the MCCB criteria. The test–retest reliability of the MCCB composite score was excellent (ICC=0.88). The severity of cognitive impairment was T =24.7 (SD=12.1) at screening and T =26.7 (SD=12.4) at baseline. The MCCB composite score demonstrated a large correlation with the UPSA-B composite score (r =.60, df =304, p <.001). The practice effect on the composite score was small (z =0.18). Discussion In the context of a 29-site antipsychotic trial in stable outpatients with schizophrenia, the MCCB is sensitive to cognitive deficits in all domains, demonstrates excellent test–retest reliability and small practice effects, and is strongly correlated with a leading measure of functional capacity.