Background. Syphilis is a systemic infection caused by T. pallidum. It continues to be reported around the world, with severe consequenc-es. In the early 2000s, a significant increase in the incidence of neurosyphilis (NS) in Russia was reported. Its diagnosis remains challenging in scientific and practice ways. Objective. To compare the effectiveness of two current approaches to laboratory diagnosis of NS: ITPA index (Intrathecal T. pallidum assay index), or serum-liquor ratio, vs. multivariate discriminant analysis (MDA). Results and discussion. Sixty-five paired biosamples (blood serum and cerebrospinal fluid) obtained from patients diagnosed with NS, including 43 from asymptomatic NS patients and 22 from symptomatic NS patients, were examined. The ITPA index was positive in 95.4% of patients, including 97.7% of asymptomatic NS patients and 90.9% of symptomatic NS patients. MDA showed 98.5% positive results, including 100% of asymptomatic NS patients and 95.5% of symptomatic NS patients. The same results of these methods were observed in 93.8% of cases. Conclusion. The high efficacy of the ITPA index and MDA in the NS diagnosis and high agreement of the two methods were demonstrated, suggesting the prospects for their use in clinical practice. © 2022, Media Sphera Publishing Group. All rights reserved.