PURPOSE: To systematically review the aetiological factors associated with molar incisor hypomineralisation (MIH). To this day, the aetiology remains unknown. Determining risk factors would allow risk assessment and enhance early diagnosis of MIH in young patients. The aim was to assess, evaluate and summarise the relationship between MIH and reported aetiological hypotheses. METHODS: Electronic database searches of MEDLINE, EMBASE, EBSCO, LILACS and Cochrane Library were conducted. Authors conformed to PRISMA guidelines. Studies were screened, data extracted, assessment of risk of bias and calibration was completed by two independent reviewers. Meta-analyses with heterogeneity calculations were performed. RESULTS: Of the potential 8949 studies, 64 studies were included in the qualitative analysis whilst 45 were included in the quantitative analysis. Prenatal factors: results are inconclusive as only unspecified maternal illnesses appear to be linked to MIH. Perinatal factors: prematurity (OR 1.45; 95% CI 1.24-1.70; p = 0.0002) and caesarean delivery (OR 1.45; 95% CI 1.09, 1.93; p < 0.00001) are associated with an increased risk of developing MIH. Birth complications are also highlighted. These three factors can lead to hypoxia, and children with perinatal hypoxia are more likely to develop MIH (OR 2.76; 95% CI 2.09-3.64; p < 0.0001). Postnatal factors: measles, urinary tract infection, otitis media, gastric disorders, bronchitis, kidney diseases, pneumonia and asthma are associated with MIH. Fever and antibiotic use, which may be considered as consequences of childhood illnesses, are also associated with MIH. Genetic factors: an increasing number of studies highlight the genetic and epigenetic influences in the development of MIH. CONCLUSION: Several systemic and genetic and/or epigenetic factors acting synergistically or additively are associated with MIH, revealing a multifactorial aetiology model. Peri- and postnatal aetiological factors are more likely to increase the odds of causing MIH than prenatal factors.