Background: Pelvic organ prolapse (POP) is the most frequent disease component in the structure of gynecological pathology (from 28 to 38.9%) and its incidence is increasing. Most of the research studies were initiated to develop various kinds of operative treatment for common prolapse cases (POP-Q III-IV); however, a large number of surgical interventions associated with a high percentage of complications and a high rate of relapses confirm the difficulty for problem-solving. In this regard, there is a need to expand ideas about the pathogenesis of the disease and develop approaches to the prediction of recurrence surgical treatment, choosing the correct and timely treatment strategy. Currently, great importance is given to the study of genetic control of connective tissue metabolism. The evidence demonstrated that polymorphism of NAT2 gene results in genetically determined disorders of connective tissue catabolism which increases the possibility of disease development approximately in 2 times. Point mutations in NAT2 lead to the so-called slow-acetylation which determines the predominance of the decay rate of collagen over its synthesis. Aim: Analyze the significance of NAT2 polymorphism as a predictor for failure of surgical treatment of pelvic organ prolapse. Materials and methods: The prospective cohort clinical trial enrolled 140 women of the reproductive age (from 28 to 42 y.o.) with symptomatic prolapse (POP-Q Stage II-III) who were examined and received treatment in the period from 2008 to 2014. All patients underwent surgical treatment of POP. The treatment included colpoperineorrhaphy with levatorplasty. In 12.9% of patients who had stress urinary incontinence - in combination with a loop urethropexies transobturatory access (Transobturator Vaginal Tape, TVT-O). Long-term results of treatment effectiveness were assessed in 3-5 years. Results: The findings revealed that the incidence rate of point mutations of NAT2 gene was >2-fold higher in patients with POP included in the ineffective treatment group (61.8%) if compared to the rate registered in the effective treatment group (30.6%). Conclusions: The obtained data indicate that the presence of point mutations in NAT2 gene is a poor prognostic factor for general types of genital prolapse and a predictor for failure of surgical treatment.