Compression of the fourth ventricle (CV4) is a well-known osteopathic procedure, utilized by osteopaths, osteopathic physicians, craniosacral therapists, physical therapists, and manual therapists as part of their healthcare practice based on some evidence suggesting impact on nervous system functions. The main objective of the study was to identify randomized controlled trials (RCTs) assessing the clinical benefits of CV4 and to show the evidence supporting clinical prescriptions, guides, and advice in treating. A computerized search of the PubMed, CINAHL Complete, Scopus, Web of Science, and ScienceDirect databases was performed. Two filters were used (article type: RCTs; species: humans). The methodological quality of the trials was assessed using the Downs and Black quality checklist for healthcare intervention studies. Only six studies met the inclusion criteria, of which four were RCTs and two were observational studies. The Downs and Black score ranged from 17 to 24 points out of a maximum of 27 points. The present review revealed the paucity of CV4 research in patients with different clinical problems, as five out of six included studies investigated healthy adults. According to the results of the included studies, CV4 may be beneficial for patients with different functional problems.