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Background: Severe immobility due to lesions of the brain necessitates therapeutic positioning over the long term. There is little scientific evidence concerning the efficacy of different positioning methods. This clinical trial compares the effects of conventional positioning (CON) with those of positioning in neutral (LiN)., Methods: A prospective, multicenter, investigator-blinded, randomized, controlled trial was performed on a total of 218 non-ambulatory patients (underlying disease: stroke, 141 patients; hypoxic brain damage, 28; traumatic brain injury, 20; other, 29). The subjects were randomly assigned to either LiN (105 patients) or CON (113 patients) and stratified within each of these two positioning concepts to five different positions. They remained in the assigned positions for two hours. The primary endpoint was change in the passive range of motion (PROM) of the hip joints. Secondary endpoints were change in the PROM of the shoulder joints and patient comfort., Results: Patients in the LiN group had a significantly better PROM of the hips after positioning than those in the CON group (difference, 12.84°; p<0.001; 95% confidence interval [CI], 5.72°-19.96°). The same was true for PROM of shoulder flexion (11.85°; p<0.001; 95% CI, 4.50°-19.19°) and external rotation (7.08°; p<0.001; 95% CI: 2.70°-11.47°). 81% of patients in the LiN group reported their comfort level as good, compared to only 38% in the CON group (p<0.001)., Conclusion: Positioning severely immobilized patients in LiN for two hours improved passive hip and shoulder mobility and patient comfort compared to conventional positioning. Further studies are needed to determine whether prolonged LiN positioning might improve rehabilitation and quality of life, prevent pressure sores, or ease nursing care.