To examine the effect of comorbidity on risk of postoperative complications, prolonged hospitalization (defined as above median length of stay), non-routine disposition, and in-patient death among women with breast cancer after surgery. Nationwide in-patient sample is a nationwide clinical and administrative database. Discharges of patients aged 40 years and older who underwent surgery for breast cancer from 2005 to 2009 were identified. Information about patients and hospitals characteristics were obtained. Comorbidities were identified and used to calculate Charlson comorbidity index (CCI) score. We divided patients based on these scores into four groups: 0, 1, 2, and ≥3. Multivariate logistic regression analyses were used to examine risk adjusted association between CCI score and the aforementioned outcomes. We identified 70,536 patients' discharges. Compared to a CCI score of zero as a reference group, CCI scores of 1, 2, and ≥3 increased the risk of post-operative complications by 1.7-fold, 2.6-fold, and 4.6-fold, respectively (p < 0.001). Patients with CCI scores of 1, 2, and ≥3 had higher risk of non-routine disposition by 1.3-folds, 1.7-folds, and 2.2-folds, respectively (p < 0.001). Patients with CCI scores of 1, 2, and ≥3 had higher risk of prolonged hospitalization by 1.2-folds, 1.6-folds, and 2.3-folds, respectively (p < 0.001). Similarly, CCI scores of 1, 2, and ≥3 increased risk of in-patient death by 3.1-folds (p 0.05), 5.4-folds (p 0.008), and 15.8-folds (p < 0.001), respectively. Comorbidity associated with worse in-hospital outcomes among women with breast cancer after surgery. Effective control of comorbidity in breast cancer patients may reduce post-operative morbidity and mortality.