AZD3480 is a selective agonist of α4β2 central neuronal nicotinic receptors (NNRs). This study investigated its effects on cognition, relative to placebo, in 440 patients with stable schizophrenia who were taking a single atypical antipsychotic medication and who were active cigarette smokers. Mean age was 41 (range 19 to 55) years and the majority of patients (88%) had a diagnosis of paranoid schizophrenia. Patients were randomized to one of 3 doses of AZD3480: 5mg, 20mg, and 35/100mg (depending on CYP2D6 metabolic status), or to placebo. Treatment was given once daily for 12weeks. The primary outcome measure was change in cognitive function from baseline to Week 12, as measured by IntegNeuro computerized test battery of cognitive function scores. Secondary outcome measures included assessment of functional capacity (University of California at San Diego Performance Based Skills Assessment [UPSA2]) and adaptive function (Social Functioning Scale [SFS]). AZD3480 failed to improve cognition relative to placebo in this population of patients or in subpopulations defined by disposition, metabolic status, antipsychotic treatment, age, age of illness onset, and sex. Likewise, no improvement relative to placebo was observed in either the SFS measure of adaptive functioning or the UPSA2 measure of functional capacity. AZD3480 was generally well tolerated in the population studied.