1513 Background: There is conflicting evidence for the effect of statins in primary prevention of colorectal cancer (CRC). We conducted a case control study (N=357,702) in non-elderly adult US population (age 18-64 years) to investigate the role of statins in primary prevention of CRC. Methods: We used MarketScan claims database to identify patients with CRC using ICD-9 codes. A case was defined as having an incident diagnosis of CRC. Up to ten controls (matched for age, sex, and geographical region) were selected per case. Statins exposure was assessed from prescriptions in the 12 months prior to the earliest date of CRC diagnosis. The primary objective was to assess the incidence of CRC in statin users and nonusers. Conditional logistic regression was used to adjust for multiple potential confounders and calculate adjusted odds ratios (AOR). Results: The mean age of CRC patients was 54 years, 52% were males.Statins were prescribed to 19.1% (68,461/357,702) patients.A total of 8.3% (5,704/68,461) patients developed CRC in statin exposed group compared to 9.3% (26,912/289,241) patients in non-statin exposed group. In a multivariate model, any statin use was associated with 25% reduced risk of CRC (AOR 0.75, 95% CI, 0.73-0.78, p<0.001). An age-stratified analysis showed more benefit in patients aged 55 years or less than those above age 56 years (AOR 0.68 and AOR 0.79 respectively; p<0.001 for interaction between age group and statin exposure). Variables associated with increased incidence of CRC in the multivariate model were obesity (AOR 1.3, 95% CI, 1.2-1.4, p<0.001); DM (AOR 1.2, 95% CI, 1.1-1.2, p<0.001); IBD (AOR 3.1, 95% CI, 2.8-3.5, p<0.001); use of insulin (AOR 1.2, 95% CI, 1.1-1.3, p<0.001) and sulfonylureas (AOR 1.2, 95% CI, 1.1-1.3, p<0.001). Prescribed NSAIDs showed modest reduction in CRC incidence (AOR 0.94, 95% CI, 0.91-0.97, p=0.002). There was no significant relationship between CRC incidence and other oral hypoglycemic drugs. Conclusions: Statins appears to reduce the incidence of CRC in non-elderly adult US population. A randomized controlled trial is needed to validate this finding.