It is widely known that outcomes after cancer surgery vary widely, depending on interactions between patient, tumor, neoadjuvant therapy, and provider factors. Within this complex milieu, the influence of complications on the cost of surgical oncology care remains unknown. The authors examined rates of Patient Safety Indicator (PSI) occurrence for 6 cancer operations and their association with costs of care. The Agency for Healthcare Research and Quality (AHRQ) PSI definitions were used to identify patient safety-related complications in Medicare claims data. Hospital and inpatient physician claims for the years 2005 through 2009 were analyzed for 6 cancer resections: colectomy, rectal resection, pulmonary lobectomy, pneumonectomy, esophagectomy, and pancreatic resection. Risk-adjusted regression analyses were used to measure the association between each PSI and hospitalization costs. Overall PSI rates ranged from a low of 0.01% for postoperative hip fracture to a high of 2.58% for respiratory failure. Death among inpatients with serious treatable complications, postoperative respiratory failure, postoperative thromboembolism, and accidental puncture/laceration were >1% for all 6 cancer operations. Several PSIs?including decubitus ulcer, death among surgical inpatients with serious treatable complications, and postoperative thromboembolism?raised hospitalization costs by ? 20% for most cancer surgery types. Postoperative respiratory failure resulted in a cost increase >50% for all cancer resections. The consistently higher costs associated with cancer surgery PSIs indicate that substantial health care savings could be achieved by targeting these indicators for quality improvement.