AimAdjuvant chemotherapy has been advised for high-risk stage II and III colon cancer since 2004. After the IDEA study showed no clinically relevant difference in outcome, reduction of adjuvant CAPOX duration from 6 to 3 months was rapidly adopted in the Dutch treatment guideline in 2017. This study investigates the real-world impact of the guideline change on overall survival (OS) and patient-reported outcomes (PROs). MethodsPatients with high-risk stage II (pT4 +) and III (pN+) colon cancer were selected from the Netherlands Cancer Registry, based on surgical resection and adjuvant CAPOX before (2015–2016) versus after (2018–2019) the guideline change. Both groups were compared on OS, using multivariable Cox regression, and on PROs. ResultsPatients treated before (n = 2330) and after (n = 2108) the guideline change showed similar OS (HR 1.02; 95 %CI [0.89–1.16]), also in high-risk stage III (pT4/N2, HR 1.06 [0.89–1.26]). After the guideline change, 90 % of patients were treated for 3 months with no inferior OS to those still receiving 6 months (HR 0.89 [0.66–1.20]). PROs 2 years after CAPOX completion, available for a subset of patients, suggest a lower neuropathy (n = 366; 26.2 [21.3–31.1] to 16.5 [14.4–18.6]) and better quality of life (n = 396; 80.9 [78.6–83.2] to 83.9 [82.8–84.9]), but no significant difference in workability (n = 120; 31.5 [27.9–35.1]) to 35.3 [33.8–36.7]), with reduction from 6 to 3 months of CAPOX. ConclusionThis real-world study confirmed that shorter adjuvant CAPOX did not compromise OS and may improve PROs, complementing the IDEA study and supporting 3 months of adjuvant CAPOX in daily clinical practice.