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Background: Screening significantly reduces mortality from colorectal cancer (CRC). Screen detected (SD) tumors associate with better prognosis, even at later stage, compared to non-screen detected (NSD) tumors. We aimed to evaluate the association between diagnostic modality (SD vs. NSD) and short- and long-term outcomes of patients undergoing surgery for CRC. Materials and Methods: This retrospective cohort study involved patients aged 50–69 years, residing in Veneto, Italy, who underwent curative-intent surgery for CRC between 2006 and 2018. The clinical multi-institutional dataset was linked with the screening dataset in order to define diagnostic modality (SD vs. NSD). Short- and long-term outcomes were compared between the two groups. Results: Of 1,360 patients included, 464 were SD (34.1%) and 896 NSD (65.9%). Patients with a SD CRC were more likely to have less comorbidities (p = 0.013), lower ASA score (p = 0.001), tumors located in the proximal colon (p = 0.0018) and earlier stage at diagnosis (p < 0.0001). NSD patients were found to have more aggressive disease at diagnosis, higher complication rate and higher readmission rate due to surgical complications (all p < 0.05). NSD patients had a significantly lower Disease Free Survival and Overall Survival (all p < 0.0001), even after adjusting by demographic, clinic-pathological, tumor, and treatment characteristics. Conclusions: SD tumors were associated with better long-term outcomes, even after multiple adjustments. Our results confirm the advantages for the target population to participate in the screening programs and comply with their therapeutic pathways. [ABSTRACT FROM AUTHOR]