ABSTRACT Background: Polycystic ovary syndrome (PCOS) is recognized as one of the most common endocrine abnormalities of human, it is characterized by hyperandrogenism, and metabolic derangement including glucose intolerance and hyperinsulinemia. Single Nucleotide Polymorphism in STK11 gene have been suggested to be associated with metformin efficacy in PCOS treated patients. Purpose: To investigate the relation of STK11 gene polymorphism (rs741765 C/T) with the response to metformin therapy for a period of three months in PCOS treated women in Karbala city. Patients and Methods: This is a prospective study for two hundred thirty-five Iraqi patients, who newly diagnosed with PCOS based on Rotterdam criteria by physician’s diagnosis during their visit to Women’s Hospital obstetrics education in Karbala /Iraq during the period from july,2019 till the end of april,2020.Patients with thyroid dysfunction, congenital adrenal hyperplasia and Cushing’s syndrome were excluded,the matched age was (18-40years). DNA extraction kit and Allele-specific polymerase chain reaction (PCR) were used for STK11 gene polymorphism, PCR product was visualized by agarose gel electrophoresis, enzymatic methods were used for blood sugar, and lipid profile measurement, LH, FSH, TSH, prolactin, total testosterone, estradiol, F.insulin were all tested by cobas e 411 analyzer, ELISA kit was used to measure SHBG. LH/FSH ratio, FAI, and HOMA-IR were calculated, all these parameters were measured for each patient and after 3-months therapy the patients had a medical checkup, identical to that before metformin giving. Results: The clinical, metabolic and endocrinal characteristics among STK11 rs741765 genotypes showed a significant differences and metformin efficacy increase as following TT>CT>CC genotypes. Conclusion: A polymorphism in STK11, a kinase gene expressed in liver and implicated in metformin action was an associated with metformin efficacy and percentage of responder women increase with number of T allele in rs741765 SNPs.