It can be challenging to study complex and novel health states within the parameters of a RCT. This report describes the use of an unblinded Phase II Clinical Trial design to investigate the effectiveness of acupuncture in the treatment of Gulf War Illness (GWI). GWI is a complex illness found among veterans of the first Gulf War, and is characterized by multiple symptoms, including fatigue, sleep and mood disturbances, cognitive dysfunction, and musculoskeletal pain. No published trials of acupuncture for the treatment of GWI exist. This trial is designed to both answer questions of the effectiveness of acupuncture for our entire sample, as well as subgroups with of individual presentations of GWI.Our primary outcome is quality of life as measured by the SF-36. In an effort to better understand this complex disease and its treatment, our multi-level measurement plan examines psychosocial variables, fatigue, sleep quality, pain, and biomarkers of inflammation and immune status. All of the measurement instruments used in this trial show good validity and reliability.This study is ongoing and clinical results are not available. We have achieved good feasibility of our recruitment, treatment, and data collection procedures.Low constraint RCT designs are an appropriate choice when investigating conditions in which the causes and mechanisms of disease are poorly understood. This naturalistic RCT includes individualized protocols, a clinically supported length and dose of treatment, a wait list control arm, and the ethical benefit that all subjects receive treatment during the study.