This systematic review and meta-analyses investigates the expression of thecell checkpoint regulator, mitotic arrest deficiency protein 2 (MAD2) in canceroustissue and examines whether an association exists between MAD2 levels and cancersurvival and recurrence. Studies investigating MAD2 expression in cancer tissueutilising immunohistochemistry (IHC) were identified by systematic literature searchesof Medline, Embase and Web of Science databases by October 2015. Random effectsmeta-analyses were performed to generate pooled hazard ratios (HRs) with 95%confidence intervals (CIs) of overall and progression-free survival according to MAD2expression. Forty-three studies were included in the overall review. In 33 studiesinvestigating MAD2 expression by IHC in cancer tissue, a wide range of expressionpositivity (11–100%) was reported. Higher MAD2 expression was not associated withan increased risk of all-cause mortality in a range of cancers (pooled HR 1.35, 95% CI0.97–1.87; P = 0.077, n = 15). However, when ovarian cancer studies were removed,a significant pooled HR of 1.59 for risk of all-cause mortality in other cancer patientswith higher expressing MAD2 tumours was evident (95% CI, 1.17–2.17; P = 0.003,n = 12). In contrast, higher MAD2 expression was associated with significant decreasedrisk of all-cause mortality in ovarian cancer patients (pooled HR = 0.50, 95% CI,0.25–0.97; P = 0.04, n = 3). In conclusion, with the exception of ovarian cancer,increased MAD2 expression is associated with increased risk of all-cause mortalityand recurrence in cancer. For ovarian cancer, reduced levels of MAD2 are associatedwith poorer outcome. Further studies are critical to assess the clinical utility of a MAD2IHC biomarker.