Non-traumatic upper extremity amputations are an increasing concern with the rising prevalence of diabetes mellitus. To ascertain the risk factors and mortality rates for these amputations, the demographic information, amputation history, comorbidities and clinical outcomes of 140 patients who underwent non-traumatic upper extremity amputations between 1 January 2004 and 31 October 2017 were studied. Correlations were assessed using Cochran-Armitage chi-squared tests, odds ratios and multivariate binomial logistic regression as appropriate. Diabetes mellitus, coronary artery disease, end-stage renal failure, peripheral arterial disease and prior lower extremity amputation were significant risk factors for multiple upper extremity amputations. One-year, 2-year and 5-year mortality rates were 12%, 15% and 38%, respectively, following first upper extremity amputation. The risk factors for upper extremity amputations correspond with those for lower extremity amputations, comprising mainly diabetes mellitus and its related comorbidities. The mortality rates for non-traumatic upper extremity amputations highlight their significant burden on patients. Level of evidence: III