Metabolic syndrome (MetS) and its components has been thought to be involved in the development of colorectal cancer (CRC). However, the results is often inconsistent according to gender or anatomical location of tumor. This study aimed to investigate the association between MetS and its components and CRC development by gender and tumor location. We evaluated the data of 22,809,722 Korean individuals of the National semi-compulsive cohort who underwent regular health check-ups between 2009 and 2012. Compared to subjects without MetS components, the hazard ratio for CRC development in patients with MetS was 1.22 (95% Confidence Interval [CI] 1.20-1.24) and this association was more prominent in men than in women (HR 1.41 95% CI 1.37-1.44 vs. HR 1.23 95% CI 1.20-1.27, P for interaction < 0.001). Left-sided colon cancers were more associated with MetS among men compared to women (HR 1.70, 95% CI 1.61-1.80 vs. HR 1.43, 95% CI 1.33-1.54), while right colon cancers showed a stronger association with MetS among women than men (HR 1.63, 95% CI 1.49-1.78 vs. HR 1.34, 95% CI 1.24-1.44) (all P for interaction < 0.001, respectively). Having two MetS components was still associated with CRC development and the association was the highest when two of glucose intolerance, abdominal obesity and low high-density lipoprotein cholesterol (HDL-C) combined. Individuals with glucose intolerance, abdominal obesity or low HDL-C levels, may need to undergo thorough screening for CRC even if they do not meet the diagnostic MetS criteria.