Background: False-negative rates (FNR) of sentinel node biopsy (SNB) after neoadjuvant chemotherapy (NAC) in node-positive (N+) breast cancer patients are <10 % when ≥3 negative SNs are obtained. Marking positive nodes has been suggested to reduce FNR. Identification of treatment effect in the nodes post-NAC is an alternative to decrease FNR. We evaluated the frequency of treatment effect in N+ patients after a pathologic complete response (pCR) with NAC. Methods: Biopsy-proven N+ patients receiving NAC were identified. Patients with nodal pCR after axillary lymph node dissection (ALND) or SNB with dual mapping and ≥3 SNs removed were evaluated for treatment effect; ALND and SNB patients were compared. Results: From January 2009 to December 2015, 528 N+ patients received NAC. Of these, 204 had a nodal pCR, 135 had an ALND, and 69 had SNB. Median age was 49 years, 15 % were hormone receptor positive (HR+)/HER2−, 27 % triple negative, and 58 % HER2+. The median number of nodes removed in ALND patients was 17 versus 4 in SNB patients. Treatment effect in nodes was identified in 192 patients (94 %) and was more common in ALND versus SNB patients (97 vs 88 %; p = .02). HR+ patients and patients without a breast pCR were less likely to have treatment effect in the nodes (p = .05). Other characteristics did not differ. Conclusions: Following NAC, SNs with treatment effect were retrieved in 88 % of patients without marking nodes, suggesting that nodal clipping may not be necessary to achieve an acceptable FNR. Longer follow-up is needed to determine regional recurrence rates in the SN-only cohort.