Abstract Background In many countries, population colorectal cancer (CRC) screening is based on age and family history, though more precise risk prediction could better target screening. We examined the impact of a CRC risk prediction model (incorporating age, sex, lifestyle, genomic and family history factors) to target screening under several feasible screening scenarios. Methods We estimated the model’s predicted CRC risk distribution in the Australian population. Predicted CRC risks were categorised into screening recommendations under three proposed scenarios to compare to current recommendations: a) highly tailored; b) three risk categories; c) four sex-specific risk categories. Under each scenario, for 35-74-year-olds, we calculated the number of CRC screens by immunochemical faecal occult blood testing (iFOBT) and colonoscopy, and the proportion of predicted CRCs over ten years in each screening group. Results Currently, 1.1% of 35-74-year-olds are recommended screening colonoscopy and 56.2% iFOBT. 5.7% and 83.2% of CRCs over ten years were predicted to occur in these groups respectively. For the scenarios: a) colonoscopy was recommended to 8.1% and iFOBT to 37.5%, with 36.1% and 50.1% of CRCs in each group; b) colonoscopy recommended to 2.4% and iFOBT to 56.0%, with 13.2% and 76.9% of cancers in each group; c) colonoscopy recommended to 5.0% and iFOBT to 54.2%, with 24.5% and 66.5% of cancers in each group. Conclusions A highly tailored CRC screening scenario results in many fewer screens but more cancers in those unscreened. Category-based scenarios may provide good balance between number of screens and cancers detected and be simpler to implement.