Background The incidence of awareness in patients undergoing general anesthesia is 0.1-0.2% in Western countries. The medical literatures about awareness during general anesthesia are still rare in China, but some previous studies have reported a higher incidence (1.4-6%) of intra-operative awareness. To find out the reason why the incidence reported in China is much higher than that in Western countries, we performed a prospective, multicenter, non-randomized observational study to determine the true incidence of intra-operative awareness in China. Methods This is a prospective, non-randomized descriptive cohort study that was conducted at 25 academic medical centers in China. Eleven thousand one hundred and eighty-five patients were interviewed by research staff for evaluation of awareness at the first and fourth day after general anesthesia with muscle relaxation. An independent blinded committee evaluated the responses and determined whether awareness occurred. Necessary data were collected for a binary logistic regression analysis. Results Data from 11,101 patients were presented. Forty-six cases (0.41%) were reported as definite awareness and 47 additional cases (0.41%) as possible awareness. Three hundred and fifty-five patients (3.19%) had dreams during general anesthesia. Awareness was associated with increased American Society of Anesthesiologists (ASA) physical status, a previous anesthesia, and anesthesia methods of total intravenous anesthesia. Conclusion The incidence of intra-operative awareness in China is approximately 0.41%, two to three times higher than that widely cited in Western countries. Inappropriately light anesthesia, and the population proportion of surgery and general anesthesia in China may account for the difference. (ClinicalTrials.gov Identifier, NCT00693875.).