Background: Organized colorectal cancer (CRC) screening programs currently cover Canadians aged ≥50 at average-risk of developing CRC and have contributed to declining CRC incidence. Rising incidence of early-onset CRC in individuals < 50 has led to lowering of the recommended screening start age to 45 rather than 50 in some jurisdictions. We used OncoSim, a publicly-available simulation tool, to model the effects of earlier screening initiation on Canadian CRC incidence, mortality and healthcare costs. Methods: OncoSim uses Canadian population and cancer registry data to simulate a representative sample of individuals from birth to death. We modeled four scenarios: no screening in average-risk individuals, screening initiation at age 50, initiation age lowered to 45 in 2022, and initiation age lowered to 40 in 2022. Each includes 32 million simulated participants. In the model, average-risk screening involves biennial FIT, available to all simulated participants regardless of family history with participation of 60% at the first recruitment attempt and 80% for repeat screening. Participants with a family history in all 4 scenarios were eligible for additional screening by colonoscopy every 5 years. Results: In our model, earlier screening yields reduced CRC incidence and mortality with increasing benefit over time. By 2051, screening initiation at age 45 or 40 reduces age-standardized incidence by 3.4% and 4.8% respectively, and age-standardized mortality by 3.3% and 4.6% respectively, compared to initiation at age 50. Screening initiation at age 45 yields 3,848 additional quality-adjusted life-years (QALYs) in 2051 at a cost of $9,350 per QALY gained and a 5% increase in colonoscopies performed. Initiation at age 40 yields 6,255 additional QALYs at $16,350 per QALY gained and a 9% increase in colonoscopies. The difference in screening costs compared to screening from age 50 is consistent year-to-year after 2024. In 2051 screening costs increase by $75mil and $155mil per year with initiation at ages 45 and 40 respectively, while costs of cancer management (including diagnosis, treatment, recurrence, palliative and end of life care) decrease by $42mil and $57mil respectively. Conclusions: Our model predicts that lowering the CRC screening initiation age for average-risk Canadians to 45 or 40 could reduce CRC incidence and mortality. Costs per QALY gained are high in the first few decades but decrease over time. Costs are modest after 30 years of screening compared to other life-preserving interventions such as dialysis. Our results suggest that lowering the screening age in Canada may be warranted, but further investigation is needed to assess capacity for increased colonoscopy demand.