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Simple Summary: Macropod Progressive Periodontal Disease (MPPD), or 'lumpy jaw', is an often-fatal dental disease commonly reported in captive kangaroos and wallabies (macropods) worldwide. The disease is difficult to treat successfully, resulting in high recurrence and mortality rates. The aim of this study was to determine animal and environmental factors that may increase the risk of developing MPPD. We conducted a multi-institution study of MPPD in macropods in zoos in Australia, and compared data with those in European zoos, where macropods are popular exhibit animals. This study reports risk factors for the development of disease including region, age, sex and particular stressors, such as transport between enclosures and between zoos. This information contributes to the understanding of disease development and advances the evidence base for preventive management strategies. We recommend protocols to reduce or prevent outbreaks of MPPD in zoos, thus decreasing morbidity and mortality rates of this challenging disease. The implementation of these recommendations will benefit the welfare and health of captive macropods worldwide. Macropod Progressive Periodontal Disease (MPPD) is a well-recognised disease that causes high morbidity and mortality in captive macropods worldwide. Epidemiological data on MMPD are limited, although multiple risk factors associated with a captive environment appear to contribute to the development of clinical disease. The identification of risk factors associated with MPPD would assist with the development of preventive management strategies, potentially reducing mortality. Veterinary and husbandry records from eight institutions across Australia and Europe were analysed in a retrospective cohort study (1995 to 2016), examining risk factors for the development of MPPD. A review of records for 2759 macropods found incidence rates (IR) and risk of infection differed between geographic regions and individual institutions. The risk of developing MPPD increased with age, particularly for macropods >10 years (Australia Incidence Rate Ratio (IRR) 7.63, p < 0.001; Europe IRR 7.38, p < 0.001). Prognosis was typically poor, with 62.5% mortality reported for Australian and European regions combined. Practical recommendations to reduce disease risk have been developed, which will assist zoos in providing optimal long-term health management for captive macropods and, subsequently, have a positive impact on both the welfare and conservation of macropods housed in zoos globally. [ABSTRACT FROM AUTHOR]