BACKGROUND: Studies have reported the effect of gender in the context of assessing predictors of survival from colorectal cancer (CRC); however, few have specifically addressed the impact of gender on the clinical and pathological outcomes of CRC. Appreciation of gender disparities may assist in the implementation of measures to address these differences, and improve the overall outcomes of patients with CRC. METHODS: The South Western Sydney Colorectal Tumour Group registry, which encompasses a population in excess of 800,000, prospectively collects data on new patients with CRC. Data from 1997 to 2004 were collected, including demography, site, grade, histopathology, stage, treatment, and survival. RESULTS: In total, 2,050 consecutive patients (44% women) with CRC were analyzed. Compared to men, women were older (median 69 yr, range 27-95 yr vs 67, range 22-92 yr, P = 0.001), had more emergency surgery for CRC-related complications (18.8% vs 15.1%, P = 0.03), had more proximal cancers (42.2% vs 31.5%, P < 0.001), had more poorly differentiated cancers (16.9% vs 12.9%, P = 0.01), and had fewer radiotherapy treatments for Dukes B and C rectal cancers (36.4% vs 48.1%, P = 0.02). Young women (aged 50 yr and below) had significantly better overall survival compared to young men; in this group, female gender predicted improved overall survival independent of age, emergency surgery, site, grade, and stage (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25-0.86, P = 0.01). Similarly, young women had significantly better cancer-specific survival (HR 0.46, 95% CI 0.25-0.85, P = 0.01). However, older women (aged over 50 yr) had worse survival independent of age, emergency surgery, site, grade, and stage (HR 1.38, 95% CI 1.14-1.68, P = 0.001). There were no gender differences in screening, histopathology, stage, or utilization of chemotherapy. CONCLUSIONS: This study demonstrated an opposing effect of gender on overall and cancer-specific survival at either side of the age of 50 yr. The protective effect of estrogen on CRC may be an important factor. Women had a greater proportion of emergency surgery, which was related to the predominance of proximal cancers in this gender. Women also had more proximal cancers, thereby limiting flexible sigmoidoscopy as a screening test.