Summary: Background: To compare the effectiveness of intermittent pneumatic compression (IPC) and/or manual lymphatic drainage (MLD) associated to compression stockings in the maintenance treatment of lymphedema. Patients and methods: Patients in the maintenance phase of lymphedema therapy with MLD and compression since more than a year with stable values for weight and circumferences of ankle and calf were asked to participate in a study: Compression had to be worn daily, (1) 4 weeks IPC+MLD, (2) 4 weeks MLD alone, (3) 4 Weeks IPC alone (Order 1 and 3 was randomized). At the beginning and after each 4 weeks, circumference measurements (by hand and by machine: BT600®, Bauerfeind) were documented, pain and discomfort were assessed, and quality-of-life questionnaires were completed. Results: Of 20 participants, 18 (14 female, 4 male), mean age 59.6 years (48–89) could be evaluated. 11 subjects had bilateral, 7 unilateral, 5 primary, 13 secondary lymphedema since 2–20 years (mean 7.7), the subjects had received MLD and compression for 2–14 years (mean 6.4), 1–3 times per week (mean 1.5). The BMI ranged between 21 and 47 (mean 33.7). No differences between any phases were found for: Calf and thigh volume, circumference of calf. Only the ankle circumference was significant less (−0.22 cm) when using “both” (IPC+MLD). Compared to before the study, quality of life was better in all three phases, but with a significantly higher improvement in the phases with IPC than in the phases without. Conclusions: There were no differences in objective measurement between MLD alone, IPC alone or both, excepting the minimal significant difference in ankle circumference after IPC+MLD. QOL favored IPC application. Considering the economic consequences of these results, a change of maintenance therapy with MLD weekly over years in favor of permanent care with IPC and few appointments of MLD per year should be considered and further investigated.