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Background Gastro-Intestinal Stromal tumours (GISTs) are rare neoplasms of mesenchymal origin that arise in the GI tract and account for approximately 0.1-3% of all GI tumours. The aim of this study was to determine whether the mode of clinical presentation of GISTs has an effect on outcome. Methods Consecutive 143 patients diagnosed with GISTs were identified from the regional network database (median age 67 (21-88) years, 85 male). Data were collected on presenting symptoms, tumour, treatment undertaken, and the primary outcome measure was survival. Results The commonest GIST anatomical sites were stomach (69.9%), small bowel (13.3%), and colon (4.9%). Commonest symptoms were abdominal pain (30.0%), dyspepsia (11.8%), and anaemia (11.1%). Symptomatic presentations were associated with older age (p = 0.056) and higher mitotic index (>5 per 50HPF, p = 0.045). On univariable analysis the factors associated with cumulative 10-year survival were age (p = 0.076), the presence of symptoms (78.1% vs. 96.4%, p = 0.028), mitotic index (p = 0.011), and modified National Institutes of Health (NIH) prognostic index (p = 0.010), but not deprivation index, anatomical site or GIST diameter. Symptomatic patients aged over 60 years with mitotic index >5 per 50 HPF had the poorest 10-year survival at 63.6% (HR 2.577, 95%CI 1.132-5.867). On multivariable analysis, NIH index (HR 4.283, 95%CI 1.395-13.149, p = 0.011) and age (HR1.061, 95%CI 1.006-1.118, p = 0.029) were independently associated with 10-year survival. Conclusions Age, symptoms, and NIH criteria represent the most important prognostic biomarkers in patients diagnosed with GISTs.