Background The absence of a functional vagina has a negative effect on the quality of life of women. Multiple surgical procedures have been described for vaginal reconstruction in these patients. Case We present a case of an 18-year-old transgender woman, who underwent laparoscopic intestinal vaginoplasty as vaginal reconstruction, and subsequently developed septic shock and multiple organ failure on the basis of an extended-spectrum β-lactamase-producing Escherichia coli. A severe progression of the necrotizing fasciitis was lethal, despite repeated surgical debridement, intravenous antibiotic use, and supportive care at the intensive care unit. Summary and Conclusion Although vaginal reconstruction has a positive influence on the quality of life in transgender women, physicians and patients need to be aware of serious complications that might arise.