Background Lactational mastitis is a maternal morbidity that affects the wellbeing of women and their babies, including through breastfeeding discontinuation. Research Aim To systematically review the available global literature on the frequency of lactational mastitis, and to summarize the evidence on risk factors for lactational mastitis. We also describe gaps in the evidence and identify priority areas for future research. Methods We systematically searched and screened 6 databases and included 26 articles, conducted meta-analysis of disease frequency, and narratively synthesized evidence on risk factors. Results In 11 (42%) articles researchers reported a measure of disease frequency; 5 (19%) reported risk factors, and 10 (39%) included both. Overall, the quality of studies was low, related to suboptimal measurement of disease frequency, high risk of bias, reverse causality, and incomplete adjustment for confounding. Meta-analysis was based on 3 studies (pooled incidence between birth and Week 25 postpartum: 11.1 episodes per 1,000 breastfeeding weeks; 95% CI [10.2–12.0]); with high heterogeneity across contexts and highest incidence in the first four weeks postpartum. Researchers assessed 42 potential risk factors; nipple damage was the most frequently studied and strongly associated with mastitis. There was a scarcity of studies from low-resource settings. Conclusions Lactational mastitis is a common condition, but the wide variability in incidence across contexts suggested that a substantial portion of this burden might be preventable. Provision of care to breastfeeding women at risk for or affected by mastitis is currently constrained due to a critical lack of high quality epidemiological evidence about its incidence and risk factors.