OBJECTIVESTo investigate the association between proximal colonic neoplasia and distal lesions as a function of the lesion type. The extent to which health, demographic, and study characteristics moderate this association was also examined.DATA SOURCESGoogle Scholar, Web of Science, Scopus, and PubMed.STUDY ELIGIBILITY CRITERIAStudies allowing the calculation of OR of proximal neoplasia(PN) and proximal advanced neoplasia (PAN) for distal hyperplastic polyps (HP), nonadvanced adenomas (NAA), adenomas (AD), and advanced neoplasia (AN); also, studies for which the proportions of subjects with isolated (i.e., not accompanied by distal lesions) PN (IPN) and PAN (IPAN) over the total number of subjects with PN or PAN could be calculated.STUDY APPRAISAL AND SYNTHESIS METHODSThirty-two studies were included for calculating OR between proximal neoplasia and distal lesions and 40 studies for proportions of IPN and IPAN. Subgroup analyses were conducted for presence of symptoms, prevalence of PN and PAN, age, proportion of males, geographic region, study design, and demarcation point.RESULTSThe association between distal lesions and proximal neoplasia increased with the severity of the distal lesions. Odds of PN were higher in subjects with HP compared to subjects with a normal distal colon. Odds of PN and PAN were higher in subjects with NAA, AD, and AN than in subjects with a normal distal colon. PAN were more strongly associated with distal lesions in asymptomatic populations, in young populations, and in populations with a low prevalence of PAN. In approximately 60% of the subjects with PN and PAN, these neoplasia were isolated.LIMITATIONSThe present results may be affected by publication bias and dichotomization in the subgroup analyses. Limitations related to the individual studies include self-selection, lesion misclassification and misses, and technological advances leading to changes in the detection of lesions during the time span of the included studies.CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGSAll types of distal lesions are predictive of PN. All types of distal neoplasia are predictive of PAN. The association between distal lesions and proximal neoplasia increases with the severity of the distal lesion. The association between distal lesions and proximal advanced neoplasia is stronger in low-risk groups as compared to high-risk groups.