Many genes associated with dopamine (DA) and norepinephrine (NE) systems influence cognitive deficits of schizophrenia patients, but one key enzyme is dopamine beta-hydroxylase (DBH), which converts DA to NE and whose activity and levels are under strong genetic control. This study examines the association of the 19bp insertion/deletion (Ins/Del) polymorphism in the 5′ flank of the DBH gene with cognitive deficits in first-episode schizophrenic patients (FEP). We assessed the cognitive function in 195 FEP and 304 healthy controls using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The 19bp Ins/Del polymorphism of DBH gene was genotyped. Our results showed that the allelic and genotypic frequencies of the 19bp Ins/Del polymorphism significantly differed between FEP and healthy controls (both p<0.05). Cognitive test scores were significantly lower in FEP than healthy controls on all scales (all p<0.001) except for the visuospatial/constructional index (p>0.05). Immediate memory abilities significantly differed by genotype (p<0.05) but not genotype×diagnosis. Immediate memory score was lower in FEP with DBH5′-Del/Del genotype (61.3±17.2) than those with DBH5′-Ins/Ins genotype (68.6±16.2; p<0.05). The 19bp Del allele was associated with poorer immediate memory performance than the Ins allele in FEP (p<0.05). However, healthy controls did not show any differences in cognitive function indices between the Ins and Del for either the allele or genotype of the 19bp Ins/Del polymorphism. Our findings suggest that the DBH5′-Ins/Del polymorphism may play a role in susceptibility to FEP. The DBH5′-Ins/Del polymorphism may also influence immediate memory in FEP. Moreover, FEP had poorer cognitive function than healthy controls in all examined cognitive domains except for the visuospatial/constructional index.