Primary lower limb lymphedema is a chronic debilitating disorder without curative treatment. The initial treatment phase is dedicated to reducing lymphedema volume, whereas the second aims to stabilize that volume. The objective of this study was to analyze clinical and lymphoscintigraphic characteristics during complete decongestive physical therapy as predictors of primary unilateral lower limb lymphedema-volume reduction. This observational, retrospective study included 222 consecutive patients (January 2009-January 2017; median age: 45.8years) with lymphedema affecting the entire lower limb, who received complete decongestive physical therapy for the first time in a specialized lymphedema management center. Complete decongestive physical therapy consisted of low-stretch bandaging, manual lymph drainage, exercises, and skin care for all patients. Lymphoscintigraphy preceded treatment. Median lymphedema evolution was 73months, and median excess volume was 34%. Median (interquartile range) lymphedema volumes were 2845 (1038-3487) mL before and 1276 (601-2195) mL after a median of 11days of complete decongestive physical therapy, with 34% median reduction. Multivariate analyses retained age, body mass index >40kg/m2, and previous cellulitis, as independently associated with lymphedema volume reduction. For each additional year of age, volume reduction increased 0.16%. Unexpectedly, log-transformed initial lymphedema volumes indicated a negative impact, that is, 4.95%, for each log-unit gain. Patients with previous cellulitis episode(s) obtained 6.9% and those with BMI>40kg/m2 17.1% higher lymphedema volume reductions. Lower limb lymphoscintigraphy was available for 150 (67.6%) patients. Having dermal back flow was associated with greater lymphedema volume reduction than not (respectively, 39% vs 31%). This study was retrospective, and only 67.6% of patients underwent lymphoscintigraphy. Our analysis identified clinical and scintigraphic predictors of primary lymphedema volume reduction for patients with unilateral disease. Lymphoscintigraphy helps confirm lymphedema and predict volume reduction. Further study is required to confirm these observations.