This systematic review summarises evidence assessing endogenous pain inhibition in people with irritable bowel syndrome (IBS) compared with healthy controls using conditioned pain modulation (CPM) and offset analgesia (OA). Evidence regarding the role of psychological variables is also examined. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Four electronic databases were searched to retrieve studies assessing CPM or OA in adults diagnosed with IBS according to the ROME II/III criteria. Standardized mean differences were calculated for each study and a random effects model was used for meta-analysis. Eleven studies were included, 5 of which reported results on the relationship between CPM and psychological variables. None of the studies assessed OA. The risk of bias assessment found a lack of assessor blinding in all studies. The pooled effect estimate was 0.90 (95% CI, 0.40-1.40) indicating a significantly lower CPM effect in people with IBS compared with controls. This effect was reduced to 0.51 when 1 outlier was excluded from the analysis. In addition, reduced CPM responses were significantly correlated with higher anxiety (r=0.17 to 0.64), stress (r=0.63), and pain catastrophizing (r=0.38) in people with IBS; however, the evidence available was limited and the strength of these associations variable. Depression was not found to be associated with CPM in these IBS cohorts. The results of this review suggest that people with IBS, as a group, demonstrate reduced pain inhibition measured by CPM. The preliminary evidence about the association between psychological factors and CPM warrants further investigations.