BACKGROUND: Low functional capacity, malnutrition, and anaemia are associated with an increased risk of complications after surgery. These high-risk indicators can be improved through preoperative interventions. The aim of the study was to examine the effect of screening for modifiable high-risk factors combined with targeted interventions on postoperative complications in patients undergoing colorectal cancer surgery. METHODS: A controlled before-and-after study was conducted including patients with colorectal cancer undergoing elective curative surgery between August 2015 and October 2018, in two institutions (intervention and control hospital). The intervention consisted of a screening for anaemia, low functional capacity, and nutritional status and their implementation (iron supplementation, prehabilitation, nutritional supplements, and consultation with a dietician), for a minimum of 4 weeks before surgery. The primary outcome was a composite measure consisting of unplanned admission to the intensive care unit, complications with Clavien-Dindo score of 3a or above, length of hospital stay less than 10 days, readmission, or death within 30 days during the postoperative course. RESULTS: A total of 1591 patients were included for analysis with 839 at the intervention hospital and 752 at the control hospital. In a difference-in-difference analysis, adjusted for age, sex, smoking, stage of disease, ASA score, surgical approach, and surgical procedure, the intervention was associated with a 10.9 per cent (95 per cent c.i. 2.1 to 19.7 per cent) absolute risk reduction of a complicated postoperative course, primarily due to a reduction in severe complications. CONCLUSION: The combined intervention of screening and prehabilitation was associated with a decreased risk of a complicated course, primarily in a reduction of severe complications.