Postoperative Ileus refers to the transient interruption of propulsive motor activity of the gastrointestinal (GI) tract that prevents effective movement of its contents and tolerance of oral intake. Although POI is generally considered to significantly increase hospital stays and inpatient costs after spinal surgery, the incidence, associated risk factors, and effective preventative strategies remain poorly characterized. The proposed etiologies underlying POI are broad and remain incompletely characterized. They include post surgical sympathetic nervous system activation, inflammatory factors, and the effects of analgesics on GI tract motility. Treatment often consists of aggressive bowel regimens, nasogastric tube insertion for decompression, and the application of various laxatives, suppositories, and enemas. The widespread use of these measures is unfortunately not supported by high level evidence. The incidence of POI after spinal fusion is reported to range between 0.6 to 16.7%. This estimated range likely represents a gross underestimate of POI given the retrospective nature of studies undertaken to date. Fineberg and colleagues reported that the risk increases nearly 3-fold following anterior lumbar spinal fusions as compared to posterior surgeries. Furthermore, the only risk factors they identified to be correlated with POI is male gender, = 3 fusion levels, alcohol abuse, anemia, electrolyte abnormalities, and weight loss. Kiely and colleagues found that ileus was associated with the administration of certain intravenous solutions such as lactated ringers and sodium chloride. Interestingly, they found that albumin administration was associated with a reduced incidence of ileus postoperatively. Lee and colleagues evaluated POI following orthopedic surgery and reported an incidence of 2.1%. They found that patients who developed POI were more likely to be older, had higher blood loss during surgery, and also had higher rates of preoperative constipation. This study, however, included all types of orthopedic surgeries (not limited to spinal fusion). Early clinical studies evaluated the effectiveness of MNTX in treating opioid-induced constipation (OIC). Several clinical trials confirmed that MNTX was well tolerated and counteracted the GI effects of opioids, thereby enhancing gut motility without inhibiting their analgesic properties. Only two studies to date have evaluated the potential effectiveness of MNTX in reducing the incidence of POI following GI surgery. Both studies were unfortunately hampered by serious design flaws. Most importantly, neither study included pre-operative administration of MNTX. As such, MNTX remains at this time approved only for chronic OIC based on two double-blind, randomized, placebo-controlled trials conducted in patients with advanced illness wherein MNTX rapidly induced laxation as compared to placebo.