OBJECTIVE: To develop and validate a comprehensive complication index (CCI) that integrates all events with their respective severity. BACKGROUND: Reporting of surgical complications is inconsistent and often incomplete. Most studies fail to provide information about the severity of complications, or inform only on the most severe event, ignoring events of lesser severity. METHODS: We used an established classification of complications, adopting methods from operation risk index analysis in marketing research to develop a formula that considers all complications that may occur in a patient. The weights of each grade of complication, defined as median reference values, were obtained from 472 participants, who rated 30 different complications. Validation to assess sensitivity to treatment effects and validity of the CCI was performed by 4 different approaches, based on 1299 patients. RESULTS: The CCI is calculated as the sum of all complications that are weighted for their severity (multiplication of the median reference values from patients and physicians). The final formula yields a continuous scale to rank the severity of any combination of complications from 0 to 100 in a single patient. The CCI was highly sensitive in detecting treatment effect differences in the context of a randomized trial (effect size detected by CCI vs conventional standardized morbidity outcomes). It also showed a negative correlation with postoperative health status (r = -0.24, P = 0.002), and high correlation with the results of patient-rated single and multiple complications on conjoint analysis (r = 0.94, P < 0.001). CONCLUSIONS: The CCI summarizes all postoperative complications and is more sensitive than existing morbidity endpoints. It may serve as a standardized and widely applicable primary endpoint in surgical trials and other interventional fields of medicine. The CCI can be readily computed on the basis of tabulated complications according to the Clavien-Dindo classification (available at www.assessurgery.com).