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Background and Aim Appendectomy is associated with various diseases, but whether it increases the risk of colorectal cancer (CRC) remains uncertain. We conducted a systematic review and meta‐analysis aimed at investigating the suggested correlation between appendectomy and CRC. Methods Systematic retrieval was performed using the PubMed, Embase, Cochrane library, Web of Science, and http://ClinicalTrials.gov databases up to May 4, 2022, for studies reported the influence of appendectomy on CRC, colon cancer (CC) or rectal cancer (RC). Odd ratios (ORs) and 95% confidence intervals (CIs) of CRC after appendectomy were pooled using the random effects model. Subgroup analyses were carried on by region, sex, and tumor location. Results Our search identified 1743 articles, of which 22 studies from three continents published between 1964 and 2022 were eligible for inclusion. Overall, people with appendectomy had a higher risk of CRC (OR = 1.31; 95% CI [1.05, 1.62]). But the risk for Europeans was not significant (OR = 0.94; 95% CI [0.87, 1.02]; I2 = 0%), while for Americans and Asians, appendectomy would increase the risk of CRC (OR = 1.68; 95% CI [1.15, 2.44]; I2 = 65% and OR = 1.46; 95% CI [1.04, 2.05]; I2 = 98%), especially in females and in developing countries. It is worth noting that appendectomy might be a protective factor for CC in European women (OR = 0.87; 95% CI [0.77, 0.98]; I2 = 0%). Conclusions Appendectomy may be a risk factor for CRC, with varying degrees in different populations. More high‐quality cross‐regional studies are needed for better clinical decision making.

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