Purpose <p>The study aimed to determine whether adjuvant chemotherapy after colorectal cancer resection is associated with an increased risk of developing incisional hernia (IH).</p> Methods <p>All patients undergoing elective curative resection of stage I-III colon adenocarcinoma between 2014 and 2017 at Copenhagen University Hospital – North Zealand were registered in a local database prospectively. This study collected additional data from patients’ electronic health records (EHR) on chemotherapy and incision placement. The follow-up computed tomography scans were retrospectively reassessed by two trained surgeons for incisional hernia for up to five years. Patients were stratified into two groups: those receiving adjuvant chemotherapy (study group) and those not receiving it (control group). The primary outcome was CT-verified IH.</p> Results <p>Of 451 patients, 303 were included in the final analysis, with 108 in the chemotherapy group and 195 in the control group. The study found that the unadjusted risk of IH was 28.9% (95% CI: 20.4–37.4) in the chemotherapy group and 21.1% (95% CI: 15.4–26.9) in the control group with an absolute risk difference of 7.7% (95% CI: -2.3–17.9, <i>p</i> = 0.13). After inverse probability of treatment weighting, the absolute risk difference was 5.6% (95% CI: -4.2–15.6), <i>p</i> = 0.26).</p> Conclusions <p>Adjuvant chemotherapy after colon cancer resection does not seem to be associated with a significantly higher risk of IH.</p> Trial registration <p>Danish Patient Safety Authority (#31-1522-51).</p>