Background and aims: Lymphatic fistulas are commonly known complications after lymph node or soft tissue resection, requiring long and sometimes difficult therapy. Doxycycline is an antibiotic agent, which was used in the treatment of pneumothoraces and pleural effusions. The aim of the study was to evaluate the effect of local doxycycline instillation on postoperative lymphatic effusions. Materials and methods: Five patients with postoperative lymphatic fistulas of different locations (inguinal, gluteal, and thoracic) were included. Patients received local doxycycline instillation after a postoperative observation period of 19-27 days without spontaneous closure of the fistulas. Results: Postoperative lymphatic fistulas closed after a single injection of doxycycline in four out of five patients within 2 days, in one patient, injection had to be repeated to achieve closure of the fistula. Drain removal was possible within 4 days after instillation in all patients; no complications occurred. Conclusions: Doxycycline can be used for treatment of persistent postoperative lymphatic fistulas in different locations. In further studies, this therapeutic concept should be evaluated with larger numbers of patients with regard to the ideal point of time, frequency, and mode of application.