Background Tissue expansion is frequently used in reconstructive surgery. Although the surgical procedure is typically considered simple, reported complication rates of tissue expansions exceed 40%. There is little evidence concerning risk factors for complications in tissue expansion in body regions other than breast. The aim was to determine risk factors for complications in non-breast tissue expansion. Methods 34 patients treated with subcutaneous tissue expanders between 2005 and 2014 were analyzed. Demographic data, body-mass index (BMI), mean arterial blood pressure (MAP), treatment indications, expansion site, previous expansion therapies in the same body region, smoking history, as well as expander characteristics (shape, volume, and filling mechanism) were ascertained. Complications were assessed and ranked according to severity based on the Clavien–Dindo classification. Binary logistic regression analysis adjusted for clinical characteristics was used. A p < 0.05 was considered as statistically significant. Results Complications were observed in 26 out of 71 expanders analyzed (36.6%), of whom 10 led to therapy failure. Expanders used in the limbs, female gender, and high expander volume turned out as significant risk factors. Patients with both a high MAP and low BMI developed tissue necrosis significantly more often (p = 0.002). The use of tissue expansion after a burn was not associated with an increased risk for complications. Conclusions This is the first study revealing female gender and low BMI as risk factors in tissue expander surgery. Thus, careful patient selection is mandatory to avoid complications in tissue expansion. Burn patients do not develop complications more often.