Anastomotic leakage (AL) is a serious complication of colorectal surgery as it greatly increases morbidity and mortality and has been associated with augmented local recurrence and diminished survival. Many risk factors have been identified to date, but sizable studies on AL after colorectal resection are lacking. This study aimed to identify the risk factors and postoperative complications of AL after colorectal surgery in the first affiliated hospital of Sun Yat-sen University. One thousand two hundred seventy-five patients who underwent colorectal cancer surgery between January 2010 and June 2013 were retrospectively studied. Twelve preoperative, 17 operative, and 11 postoperative variables were examined by the chi-square test or Fisher's exact test for univariate analysis and were then further examined by multivariate logistic regression analysis, among which one operative and three postoperative variables were examined in 426 rectal cancer surgeries. Additionally, eight postoperative complications and short-term prognostic variables were also examined by the chi-square test or a Fisher's exact test. AL was identified in 60/1158 (5.2%) total patients, 20/732 (2.7%), and 40/426 (9.4%) of whom had colonic and rectal cancer, respectively. Univariate analysis identified preoperative variables: sex (p=0.012), preoperative carcinoembryonic antigen (CEA) level (p<0.001), and hemoglobin level (p=0.089); operative variables: surgical time (p=0.009), anastomotic methods (p=0.003), surgical staging (p=0.016), and operative sites (p<0.001); and postoperative pathologic variables: distance from tumor to distal incisional margin (p<0.001). For rectal cancer, the variables included rectal procedures (p=0.022), rectal segments (p=0.010), distance from the tumor to the dentate line (p=0.011) and total mesorectal excision (TME) (p=0.046). All of these variables were included in the multivariate analysis, which identified the surgical time (p=0.021), preoperative CEA level 41g/L (p<0.001), and double-stapled anastomosis (p=0.007); for rectal cancer, the middle or lower rectal segment (p=0.008, 0.005, respectively) was included as an independent predictive factor for AL. Of the eight postoperative complications or short-term prognostic variables, postoperative hospital stay, abdominal infection, urologic infection, and incisional infection were considered significant. The rate of AL after rectal cancer is much higher than that of colon cancer. Surgical time, tumor biomarkers, anastomotic methods, and rectal segments may have the potential to increase the occurrence of AL. Additionally, AL may increase patients' hospital costs, length of stay and other relevant complications.