Abstract <p>The article presents the results of a long-term study, the purpose of which was a comparative assessment of the impact of long-term exposure to weightlessness on indicators characterizing the functional state of the human musculoskeletal system. The study involved 18 cosmonauts (<i>M</i> ± <i>SD</i>: 44.1 ± 5.3 years, 81.6 ± 7.5 kg, 179.8 ± 5.1 cm) who had completed long-term space flights on the <i>International Space Station</i> (<i>ISS</i>) lasting 178 ± 16 days (<i>M</i> ± <i>SD</i>). The functional state of the musculoskeletal system before and after space flights was assessed based on biomechanical characteristics of walking at a pace of 90 steps/min: kinematic, electromyographic, and spatiotemporal. The article presents the results of the analysis of biomechanical characteristics of walking before and after space flights of the combined group of cosmonauts (<i>n</i> = 18). For the first time, an assessment was made of the dynamics of restoration of biomechanical characteristics of walking in the post-flight period of three groups of cosmonauts, distributed depending on the volume and intensity of physical training on a treadmill during long-term space flights. The results of the study revealed significant changes in the state of the musculoskeletal system as a result of being in conditions of weightlessness. During walking at a pace of 90 steps/min in the post-flight period, the kinematic (joint angles, torso inclination), electromyographic (EMG cost of shin muscle work) and spatiotemporal (length and duration of a double step) walking parameters changed. The key factor that determines the indicated changes in locomotion in the post-flight period is the reduction and elimination of the required level of support loads during space flights. Analysis of the dynamics of recovery of some biomechanical characteristics of locomotion (EMG-cost of shin muscle work, double step length) depending on the volume and intensity of physical training during space flights showed that prevention of negative consequences of the influence of weightlessness depends on rational use of physical training. The optimal combination of volume and intensity of training loads, as well as adherence to the principles of intervals and cyclicity are key factors in the positive dynamics of the recovery of walking characteristics after the return of cosmonauts to Earth.</p>