Syphilis is an infectious disease caused by pale treponema, transmitted mainly through sexual contact (STDs). The disease is characterized by lesions of the skin, mucous membranes, internal organs, nervous and musculoskeletal systems; in addition, it is characterized by a staged, recurrent and progressive course. Currently, there is an increase in the number of patients with serological resistance, which is characterized by persistent positive non-treponemal tests without a tendency to decrease antibody titers for 12 months after adequate therapy. Serological resistance leads to rapid disability of patients or their death. The aim of this research was to study the factors of seroresistance formation in patients with syphilis who have undergone a full course of specific therapy with various drugs in the Yakutsk Republic’s Dermatovenerological Dispensary. The study covered 57 patients with seroresistance in the period 2002–2024. Thus, the prevalence of seroresistance among patients with syphilis in the Sakha Republic (Yakutia) made 0.5 %. The average age was 41+12.9 years; by gender, women predominated with 57.1 %. As a primary diagnosis in patients with seroresistance, latent early syphilis with 66.7 % predominated. Serological resistance formed on average after 28 months. Primary treatment of patients with syphilis with reserve drugs from the group of the 3rd generation cephalosporins was received by 59.6 % of the patients, and with penicillin drugs – 40.4 %. Almost the same data were obtained in the treatment of the patients with serological resistance, which amounted to 60 % and 40 %, respectively. In the structure of concomitant diseases, viral hepatitis was noted in 7 %, STIs – in 3.5 %, HIV – in 1.8 % of the patients.