Patients who achieve a pathological complete response (pCR) after neoadjuvant therapy, including chemotherapy with or without trastuzumab (NAT) have better outcomes than patients with residual disease. Despite the excellent prognosis associated with achieving a pCR, tumors still recur. The objective of this study was to evaluate factors associated with tumor recurrence and survival among patients achieving pCR after NAT. We identified 749 patients with primary breast cancer who achieved pCR after NAT between 1988 and 2009. pCR was defined as no evidence of invasive cancer in the breast and ipsilateral axillary lymph nodes on pathological evaluation. The Kaplan-Meier product limit method and multivariate Cox proportional hazards models were used to determine the association between clinical and demographic factors and outcomes. Median follow-up was 35 months (range, 1-258 months). Overall 5-year distant metastasis-free survival was 93% (95% confidence interval [CI], 90-95%) and 5-year overall survival (OS) was 96% (95% CI, 93-97%). In the multivariable model, we observed that patients >50 years had significantly decreased risk of distant metastasis (hazard ratio [HR] 0.47; 95% CI, 0.22-0.98) and that patients with clinical stage at diagnosis IIIB-C cancer had both an increased risk of distant metastasis (HR 3.92; 95% CI, 1.54-10.00) and lower OS (HR 4.75; 95% CI, 1.60-14.08). Patients with pCR after NAT have excellent outcomes. However, our data show that younger patient and those with clinical stage at diagnosis IIIB and IIIC cancers are at increased risk of developing distant metastasis.