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ABSTRACT Background: The superior mesenteric artery (SMA) syndrome is a rare cause of proximal intestinal obstruction caused by vascular compression of the third part of the duodenum between the aorta and the SMA. The syndrome can be diagnosed based on hypotonic barium duodenography (HBD) or computed tomography (CT) of the abdomen. Medical treatment consisting of prokinetics and artificial feeding and surgical treatment including duodenojejunostomy, Strong’s procedure and gastroenterostomy are possible. Different success rates are reported, the best therapeutic strategy is yet not defined. Moreover, the relevance of the syndrome as the cause of symptoms is still controversial. Methods: We performed a retrospective chart review on all patients who underwent a HBD for a clinical suspicion of SMA syndrome between January 2003 and September 2017. Symptoms, weight, diagnostics, treatment and effect of treatment on weight and symptoms were analyzed. All HBD studies were revised to obtain a standardized protocol. SMA syndrome was diagnosed when the two criteria were fulfilled: 1/ a fixed, non-resolving and abrupt narrowing of the duodenum and 2/ a proximal duodenal dilatation. CT images were revised to measure the aortomesenteric distance (AMD) and aortomesenteric angle (AMA). Results: Forty-nine patients underwent a HBD (33.2±1.6 years; 84% female; BMI 17.5 (16,5, 19.1) kg/m2). Nausea (71%) and vomiting (60%) were the most frequent symptoms leading to the test. The majority reported weight loss (86%). After exclusion of other, more likely diagnoses, eleven patients were found to have HBD-confirmed SMA syndrome. The clinical characteristics of the cases were very similar to the controls. The AMA (18.8° ± 2.52 vs 26.5° ± 2.11; p = 0.05) was significantly reduced compared to the patients with a negative HBD. The AMD was comparable in cases and controls (6.11 ± 0.68 mm vs 7mm (6, 9); p = 0.13). Gastric emptying studies showed significantly slower gastric emptying for solids in controls compared to cases with SMA syndrome (half emptying time 119min (74, 159) vs 70min (64.5, 85.5); p = 0.02). Medical treatment was administered as the sole treatment in 55% of the cases with weight gain in 67% and a subjective favorable, rather favorable or globally unchanged outcome in 17, 33 and 50% respectively. Patients were treated surgically in 45% of the cases with weight gain in 80% and a subjective favorable or globally unchanged outcome in respectively 20 and 80%. Conclusion: SMA syndrome remains a difficult and controversial diagnosis, which is often suspected in patients with chronic gastrointestinal symptoms, especially refractory nausea and vomiting, but also epigastric pain, in combination with weight loss, typically in an underweight patient. The combination of a suggestive clinical presentation with a positive HBD is required for diagnosis while CT and MRI can support the diagnosis based on a shorter AMD and/or smaller AMA. Based on our series, the effect of surgical treatment is limited and we suggest medical therapy with a focus on weight gain. Hence, in the overall majority of cases, the diagnosis of SMA syndrome does not affect subsequent management.