Pharmacogenetic studies in schizophrenia patients illustrated variable response to antipsychotic treatment. Moreover, most of patients will require long-term use of atypical antipsychotic medications which may lead to drug side effect, treatment-resistance, medication arrest, and even venture to suicide. Clozapine is the best choice in the treatment of refractory patients, although not effective in all of them and also having side effects. Therefore, any information that help to predict the outcome of each antipsychotic drug in a particular patient will be highly valuable to find the right drug for the right patient. Taq1A (rs1800497) polymorphism of dopamine receptor D2, T102C (rs6313) and His452Tyr (rs6314) polymorphisms of serotonin 2A receptor were analyzed as effective single nucleotide polymorphisms (SNPs) associated with clozapine response in schizophrenia patients in an ethnic group of Iranian population. Our data suggest that the presence of C allele for rs1800497 and rs6314 and T allele for rs6313 might be helpful for determining response to clozapine in first line therapy resistant patients. 37% of patients who had the above polymorphic alleles together, manifested improved response to clozapine versus 1.6% of clozapine responder patients who did not carry those alleles. Our data confirm that these polymorphisms are associated with clozapine response in schizophrenia patients in the studied population. Genetic screening of these three effective SNPs may be advantageous to predict clozapine response in Iranian schizophrenia refractory patients.