Background After publication of the findings of the American College of Surgeons Oncology Group Z1071 trial, sentinel lymph node biopsy (SLNB) has been increasingly performed in patients with breast cancer after neoadjuvant chemotherapy (NAC). Purpose To investigate the pretreatment breast MRI and clinical-pathologic characteristics associated with failed sentinel node identification after NAC in patients with breast cancer. Materials and Methods Patients who underwent SLNB after NAC between January 2015 and January 2019 were retrospectively identified. Two radiologists independently reviewed the characteristics of axillary nodes (number, perinodal infiltration, cortical thickness, and maximal diameter) at pretreatment breast MRI. The associations of the clinical-pathologic and imaging characteristics of the axillary nodes with sentinel node identification were assessed by using the χ2 test and/or the χ2 test for trend and multivariable logistic regression with odds ratio (OR) calculation. Results A total of 276 women (mean age ± standard deviation, 48 years ± 9; range, 27-68 years) were included. Sentinel nodes were identified in 252 of the 276 patients (91%). Multivariable analysis showed that higher (stage 3 or 4) clinical T stages (OR = 5.2, P = .004 for radiologist 1; OR = 4.6, P = .01 for radiologist 2), use of a single tracer (OR = 4.3, P = .04 for radiologist 1; OR = 3.9, P = .046 for radiologist 2), a greater number (10 or more) of suspicious axillary nodes (OR = 11.5, P = .002 for radiologist 1; OR = 8.3, P = .01 for radiologist 2), and the presence of perinodal infiltration (OR = 7.0, P = .002 for radiologist 1; OR = 7.5, P = .003 for radiologist 2) were associated with failed sentinel node identification. Conclusion A greater number of suspicious axillary nodes and the presence of perinodal infiltration at pretreatment MRI, higher clinical T stages, and use of a single tracer were independently associated with failed sentinel node identification after neoadjuvant chemotherapy in patients with breast cancer. © RSNA, 2020 See also the editorial by Imbriaco in this issue.