Background In schizophrenia, neurocognitive deficits associated with the illness are modulated by tobacco smoking. However, little is known about how smoking status modulates the relationships between neurocognitive measures in schizophrenia and healthy control subjects. Objective The goal of this study was to evaluate the relationship between sensorimotor gating assessed by prepulse inhibition (PPI) and executive cognitive function using the Wisconsin Card Sorting Test (WCST) in schizophrenia and controls as a function of smoking status. Method We studied PPI and neuropsychological function in four groups (N =50); smokers with schizophrenia (SS; n =15), control smokers (CS; n =13), non-smokers with schizophrenia (SNS; n =11) and control non-smokers (CNS; n =11). Results SNS demonstrated the poorest PPI, while SS showed comparably high levels of PPI to CNS. Non-psychiatric controls outperformed patients on WCST outcomes irrespective of smoking status. Several prefrontal outcome measures on the WCST (categories completed, percentage perseverative and non-perseverative errors) correlated significantly with PPI at the 60 and 120 ms prepulse intervals. In contrast, there were no significant correlations between PPI and any WCST outcomes in SNS, CS or CNS, and few significant correlations between PPI and other neuropsychological measures. Discussion Our preliminary data suggests that the correlation between sensorimotor gating (PPI) and prefrontal executive cognitive functioning (WCST) is enhanced by acute cigarette smoking in schizophrenia.