Finding additional ways to manage lymphedema due to lymphatic filariasis (LF) is a primary concern for the Global Program to Eliminate Lymphatic Filariasis. The WHO-recommended Essential Package of Care (EPC) consists of skin hygiene, elevation of affected limbs, exercise, protective shoe ware, wound care, and supportive therapy for acute phases. The care program has been successful but often hard to maintain. A double-blind study reexamined previous findings that doxycycline treatment could improve the lymphedematous changes in LF patients. The present study was carried out in a semi-urban location of Kerala, southern India, where Brugia sp. is the predominant parasite, and LF mass drug administration had ceased in many areas. Two hundred individuals (aged 14-65 years; 142 females and 58 males) with lymphedema of stages 1-3 were instructed in the EPC and were randomly administered either 200 mg doxycycline or an identical-appearing placebo daily for 6 weeks. Data were collected at 0, 3, 6, 12, 18, and 24 months and included the state of the lymphedema (size, cleanliness, skin thickness and changes), occurrence of adenolymphangitis (ADL) attacks, and patients' quality of life (QOL). The results demonstrated no difference over time between the two arms of the study; virtually all patients of both groups showed either improvement or "no worsening" in the parameters during the 2-year study period. Importantly, this rigorous trial confirmed that the EPC is of substantial benefit to lymphedema patients by reducing acute ADL and improving their QOL and clinical condition.