We evaluated whether the sequence or regimen of systemic chemotherapy could be a risk factor for breast cancer-related lymphedema (LE). We retrospectively analyzed 848 patients with stage II/III breast cancer who underwent curative surgery with adequate systemic therapy from 2004 to 2009. Adjuvant chemotherapy (ACT) was performed in 552 patients (65.1 %) and neoadjuvant chemotherapy (NAC) in 296 (34.9 %). We evaluated the incidence of LE based on clinicopathological factors and treatments. At a median follow-up of 5.1 years, 358 patients (42.2 %) had experienced LE and 243 (28.7 %) had retained (persistent LE) [120/552 (21.7 %) with ACT vs. 123/296 (41.6 %) with NAC; P < 0.001]. The incidence of LE in patients with taxane was greater than in those without taxane [233/704 (33.1 %) vs. 10/144 (6.9 %); P < 0.001]. Multivariate analysis showed that NAC [hazard ratio (HR), 1.63 in LE event; P < 0.001; HR, 1.39 in persistent LE; P = 0.02] and RT including supraclavicular area (SCRT) (HR 1.55; P = 0.02; HR 1.93; P = 0.006), number of dissected axillary lymph nodes (N-ALNs) >10 (HR, 1.37; P = 0.01; HR, 1.71; P = 0.001), advanced stage (HR, 1.31; P = 0.03; HR, 1.60; P = 0.002), and taxane (HR, 1.69; P = 0.03; HR, 2.07; P = 0.04) were independent risk factors for the LE occurrence. In addition to advanced stage, N-ALNs and SCRT, NAC, and taxane were shown to increase the risk of LE, which could help clinicians identify patients at risk for LE.