Context There is a paucity of research assessing the efficacy of osteopathic manipulative treatment (OMT) in patients with vertigo. Objective To assess the feasibility of conducting a randomized, controlled trial comparing OMT and vestibular rehabilitation therapy (VRT), alone or in combination, in patients with vertigo and somatic dysfunction. Methods Volunteers with vertigo who were also diagnosed with somatic dysfunction (SD) were prospectively enrolled in a blinded, randomized, controlled cohort comparative effectiveness study and assigned to 1 of 4 groups: OMT alone, VRT alone, a combination of OMT and VRT (OMT/VRT), or a nonintervention control group. Participants between 18 and 79 years of age were included if they had experienced symptoms of vertigo for at least 3 months’ duration, demonstrated somatic dysfunction, and could participate in computerized dynamic posturography (CDP) testing, tolerate manual therapy and exercises, and communicate effectively in English or Spanish. A total of 3 treatments lasting 45 minutes each were administered 1 week apart to each participant. OMT in this study consisted of counterstrain, myofascial release, balanced ligamentous tension, soft tissue, HVLA, and articulatory techniques. Comparisons were made between composite scores (CS) assessed with computerized dynamic posturography (CDP), dizziness handicap inventory (DHI), optometric evaluation, and osteopathic structural examinations collected before the first treatment, after the third/final treatment, and 3 months after the final treatment. (ClinicalTrials.gov number NCT01529151) Results A total of 23 patients were included in the study: 7 in the OMT group, 5 in the VRT group, 6 in the OMT/VRT group, and 5 in the control group. The OMT/VRT group demonstrated significant improvement in DHI score (P=0.0284) and CS (P=0.0475) between pre- and 3-month posttreatment measures. For total severity, improvements were significant in the OMT group both from pretreatment to immediate posttreatment measures (P=0.0114) and from pretreatment to 3-month posttreatment measures (P=0.0233). There was a statistical difference between the OMT and control groups from pretreatment to 3-month posttreatment DHI scores (P=0.0332). Also, there was a statistical difference in DHI score between VRT and control from pre- to 3-month posttreatment scores (P=0.0338). OMT/VRT statistically and clinically improved visual acuity in patients’ right eyes from pre- to posttreatment (P=0.0325). In all participants, vergence dysfunction was prevalent (5; 21.7%) in addition to vertical heterophoria (15; 65.2%). Conclusion A combination of OMT and VRT significantly reduced vertigo and improved balance 3 months after treatment (P<0.05). There was a high prevalence in vergence and vertical heterophoria, which are not typical screening measurements used by physical therapists and physicians to assess vertigo patients. With a small sample size, this study demonstrated the feasibility of an interdisciplinary team evaluating and treating patients with vertigo in a community setting. A larger study is needed to assess the efficacy of OMT/VRT in vertigo patients.