Colorectal cancer (CRC) is the third most common cancer worldwide. Population-based, high-resolution studies are essential for the continuous evaluation and updating of diagnosis and treatment standards. This study aimed to assess adherence to clinical practice guidelines and investigate its relationship with survival. We conducted a retrospective high-resolution population-based study of 1050 incident CRC cases from the cancer registries of Granada and Girona, with a 5-year follow-up. We recorded clinical, diagnostic, and treatment-related information and assessed adherence to nine quality indicators of the relevant CRC guidelines. Overall adherence (on at least 75% of the indicators) significantly reduced the excess risk of death (RER) = 0.35 [95% confidence interval (CI) 0.28–0.45]. Analysis of the separate indicators showed that patients for whom complementary imaging tests were requested had better survival, RER = 0.58 [95% CI 0.46–0.73], as did patients with stage III colon cancer who underwent adjuvant chemotherapy, RER = 0.33, [95% CI 0.16–0.70]. Adherence to clinical practice guidelines can reduce the excess risk of dying from CRC by 65% [95% CI 55–72%]. Ordering complementary imagining tests that improve staging and treatment choice for all CRC patients and adjuvant chemotherapy for stage III colon cancer patients could be especially important. In contrast, controlled delays in starting some treatments appear not to decrease survival