Background: The neutrophil to lymphocyte ratio (NLR) has been reported that is associated with response to treatment and prognosis in breast cancer, but its role is unclear in HER2 positive breast cancer. In this study, the relevance of NLR for treatment efficacy was analyzed in HER2 positive breast cancer patients underwent neoadjuvant therapy. Methods: Pre-treatment NLR was assessed in 546 HER2 positive breast cancer patients divided into three groups according to neoadjuvant treatment regimens: i) chemotherapy alone, ii) chemotherapy plus trastuzumab, and iii) chemotherapy plus trastuzumab and pertuzumab. The cutoff value of NLR was defined as 2.75. We evaluated the correlation of NLR with pathologic complete response (pCR) rate to neoadjuvant treatment regimen. Results: Of all patients, 422 (77.3%) patients were classified as low NLR group (NLR < 2.75) and 124 (22.7%) patients as high NLR group (NLR≥2.75). In the low NLR group, a pCR was achieved in 59 (25.7%) of 230 patients with chemotherapy alone, 69 (57.5%) of 120 patients with chemotherapy plus trastuzumab, and 47 (65.3%) of 72 patients with chemotherapy plus trastuzumab and pertuzumab (P< 0.001). In the high NLR group, a pCR was achieved 13 (18.8%) of 69 patients with chemotherapy alone, 5 (20.0%) of 25 patients with chemotherapy plus trastuzumab, and 18 (60.0%) of 30 patients with chemotherapy plus trastuzumab and pertuzumab in the high NLR group (P< 0.001). The pCR rate of chemotherapy plus trastuzumab and chemotherapy plus trastuzumab and pertuzumab was similar, but higher than chemotherapy alone in patients with low NLR. However, only chemotherapy plus trastuzumab and pertuzumab showed high pCR rate compared to chemotherapy alone and chemotherapy plus trastuzumab in patients with high NLR, regardless of hormone receptor status. The elevated NLR was an independent predictor of low pCR rate in patients with chemotherapy plus trastuzumab (OR 0.18, 95% CI, 0.07 to 0.52; P= 0.002), but not in those with chemotherapy alone (OR 0.67; 95% CI, 0.34 to 1.32; P= 0.248; P_interaction= 0.041) and chemotherapy plus trastuzumab and pertuzumab (OR 0.80; 95% CI, 0.33 to 1.92; P= 0.614; P_interaction= 0.031). Conclusions: This study identified a possibility of NLR as an easily accessible predictive marker to guide neoadjuvant HER2 target therapy in HER2 positive early breast cancer. Further study with other cohort is needed for validation.