Decision making ability has been reported to be impaired in schizophrenia patients, but no research has examined the genetic bases of this impairment. This study investigated how decision making was affected by the genetic variants in the serotonin transporter gene (triallelic 5- HTTLPR) and serotonin receptor 1A gene (rs6295) and their interaction in 465 schizophrenia patients and 448 healthy controls. The Iowa Gambling Task (IGT) was used to evaluate decision making under ambiguity (the first 40 trials) and decision making under risk (the last 60 trials). Results showed that, among the patients, the main effects of 5- HTTLPR (F(2) (,16) = 6.54, P = 0.002) and HTR1A rs6295 (F(2) (,16) = 3.87, P = 0.021) polymorphisms and their interaction effect (F(4) (,16) = 3.32, P = 0.005) were significant for the first 40 trials, with the GG genotype of HTR1A rs6295, the L'L' genotype of 5- HTTLPR and the GG-L'L' combination showing poorer IGT performance than their counterparts. Results for the healthy controls showed a similar pattern but did not reach statistical significance. No significant effects were found for the last 60 trials. These results are discussed in terms of their implications for our understanding of the genetic mechanisms of decision making in schizophrenia patients as well as healthy adults.