Introduction . Piriformis syndrome (PFS) refers to tension of the piriformis muscle followed by compression of the sciatic nerve in the sciatic foramen. PFS occurs in 6-35 % of patients with low back pain. Such a dispersion can be explained by the difficulty in PFS diagnosing and its frequent non-detection against the background of concomitant masking pathologies. Despite the great progress in PFS research, much remains unclear. This concerns first of all the clarification of epidemiological data, risk factors and optimal treatment regimens. The widely used drug therapy does not always lead to the achievement of the required results, and it dictates the need searching for new therapy methods. Manual therapy has been successfully used for a long time in the treatment of patients with this nosology, however, most often, as an addition to the ongoing pharmacotherapy. Evaluation of the effectiveness and objectification of the manual treatment methods using as monotherapy has been little studied. The goal of research — to study the clinical effectiveness of the manual therapy and pharmacotherapy in the treatment and rehabilitation of patients with piriformis syndrome. Materials and methods . The study was conducted in 2018-2019 on the clinical basis of the Department of Sports Medicine and Medical Rehabilitation of the Federal State Autonomous Educational Institution of Higher Education I. M. First Moscow State University Sechenov (Sechenov University). The study involved 40 patients. All participants were divided into two equal groups. In the main group (group I), patients were treated with manual therapy methods, in the other group (group II), only pharmacotherapy was used. Results . The use of manual therapy in patients with piriformis syndrome leads to a significantly more pronounced decrease in the degree of pain syndrome and normalization of impaired muscle tone, in comparison with pharmacotherapy. Complications and negative reactions during treatment and after the application of methods of manual influence were not observed in all cases. Conclusion . There was a positive trend in the use of manual therapy methods for the treatment and rehabilitation of patients with piriformis syndrome in this study. It allows recommending the use of manual methods of treatment in patients with this nosology.