ObjectiveTo compare the effectiveness of single-stage vascularized lymph node transfer (VLNT) combined with lymphaticovenular anastomosis (LVA) and liposuction (LS) (3L) versus LVA combined with LS (2L) for the treatment of moderate-to-late stage upper limb lymphedema following breast cancer surgery. Methods A retrospective analysis was conducted on the clinical data of 16 patients with moderate-to-late stage upper limb lymphedema after breast cancer surgery, treated between June 2022 and June 2024, who met the selection criteria. Patients were divided into 3L group (n=7) and 2L group (n=9) based on the surgical approach. There was no significant difference (P>0.05) in baseline data between the groups, including age, body mass index, duration of edema, volume of liposuction, International Society of Lymphology (ISL) stage, preoperative affected limb volume, preoperative circumferences of the affected limb at 12 levels (from 4 cm distal to the wrist to 42 cm proximal to the wrist), preoperative Lymphoedema Quality of Life (LYMQoL) score, and frequency of cellulitis episodes. The 2L group underwent LS on the upper arm and proximal forearm and LVA on the middle and distal forearm. The 3L group received additional VLNT in the axilla, with the groin serving as the donor site. Outcomes assessed included the change in affected limb volume at 12 months postoperatively, and comparisons of limb circumferences, LYMQoL score, and frequency of cellulitis episodes between preoperative and 12-month postoperative. Ultrasound evaluation was performed at 12 months in the 3L group to assess lymph node viability. Results Both groups were followed up 12-20 months, with an average of 15.13 months. There was no significant difference in the follow-up time between the groups (t=–1.115, P=0.284). All surgical incisions healed by first intention. No adverse events, such as flap infection or necrosis, occurred in the 3L group. At 12 months after operation, ultrasound confirmed good viability of the transferred lymph nodes in the 3L group. Palpation revealed significant improvement in skin fibrosis and improved skin softness in both groups. Affected limb volume significantly decreased in both groups postoperatively (P<0.05). The reduction in limb volume significantly greater in the 3L group compared to the 2L group (P<0.05). Circumferences at all 12 measured levels significantly decreased in both groups compared to preoperative values (P<0.05). The reduction in circumference at all 12 levels was better in the 3L group than in the 2L group, with significant differences observed at 7 levels (8, 12, 16, 30, 34, 38, and 42 cm) proximal to the wrist (P<0.05). Both groups showed significant improvement in the frequency of cellulitis episodes and LYMQoL scores postoperatively (P<0.05). While the improvement in LYMQoL scores at 12 months did not differ significantly between groups (P>0.05), the reduction in cellulitis episodes was significantly greater in the 3L group compared to the 2L group (P<0.05). Conclusion The combination of VLNT+LVA+LS provides more durable and comprehensive outcomes for moderate-to-late stage upper limb lymphedema after breast cancer surgery compared to LVA+LS, offering an improved therapeutic solution for patients.