Currently, there is increased incidence of neurosyphilis (NS) in the In Russian Federation, often resulting in patient’s disability and even death. However, current laboratory diagnostic methods for NS often have low diagnostic efficacy, which makes it necessary to find new diagnostic approaches. Objective. This study is aimed at conducting a comparative analysis of scheduled and nonscheduled diagnostic methods for NS and experimental testing of immunochip-based innovative technologies. Material and methods. We analyzed the blood serum and cerebrospinal fluid (CSF) of 49 patients with NS and 24 control subjects, who do not have syphilis. The patients underwent immunochemical tests of the blood serum and CSF analysis, including assessment of total protein and cell count, scheduled non-treponemal and treponemal tests, as well as VDRL method (Venereal Disease Research Laboratory), which is not scheduled in the Russian Federation, in order to establish NS diagnosis. Diagnostic efficacy of the experimental batch of immunochips (aldehyde-activated glass slides having microzones (arrays) on their surface with “printed” diagnostically relevant immunodominant antigens of Treponema pallidum: Tp47, Tp17, Tp15) have been approbated and assessed in NS patients. Results. The analysis of blood serum samples from NS patients showed that diagnostic sensitivity, specificity, and efficacy was 97.9, 100, and 98.6%, respectively, for of VDRL and 100% for microprecipitation test (MPT). Diagnostic sensitivity of treponema-specific methods, including immunochips technique, was 100%. Diagnostic specificity and diagnostic efficacy of enzyme immunoassay (ELISA) and immunochips were 100%. General clinical tests of CSF samples showed low sensitivity (cell count — 27%, protein — 30.6%). Non-treponemal tests had low sensitivity (MPT — 12.2%; VDRL — 38.8%) despite their high specificity (100%). However, the sensitivity of VDRL was 3 times higher compared to MPT in patients with all NS forms, 4 times higher in the diagnosis of asymptomatic NS, and 6 times higher in the diagnosis of NS with symptoms. Among the treponemal tests, the highest sensitivity was found for ELISA (98%), modification of immunofluorescence test with whole SCF (100%), and immunochips (100%). Diagnostic specificity of ELISA and immunochips was 100%, diagnostic efficacy was 98.6 and 100%, respectively. CSF analysis using immunochips detected antibodies to Tp17 antigen in 100% of the samples, to various combinations of two or more antigens — in 85.7% of samples. Conclusions. It was found that non-treponemal VDRL has higher diagnostic efficacy than MPT in the blood serum and CSF tests of NS patients and therefore it is advisable to include this methods in the list of scheduled diagnostic methods for NS. Immunochip, containing 4 recombinant antigens of Treponema pallidum (Tr17, Tr15, Tr47, TmpA) can also be successfully used in clinical medicine for the diagnosis of NS, as evidenced by high level of its diagnostic efficacy in the analysis of blood serum and CSF samples of NS patients.