We systematically reviewed whether the number of teeth is related to all-cause or circulatory mortality and whether replaced teeth are protective against all-cause or circulatory mortality. The search was based on the PubMed database. All cohort studies published in peer-reviewed journals were selected. Studies on periodontal disease and mortality were excluded if they did not provide information on the number of teeth. Risk estimates from studies with appropriate exposure definition, confounder adjustment and sample size were included in a meta-analysis. Three high-quality studies found a relationship between the number of teeth and circulatory mortality, whereas a moderate study did not. Two out of four moderate- to high-quality studies reported a relationship between the number of teeth and all-cause mortality. No study has investigated whether replaced teeth are protective against mortality. Therefore, denture use was taken as proxy. The methodological quality of studies on denture use and mortality was generally low to moderate. The findings of two moderate studies indicated an effect of prosthodontic replacements on all-cause mortality, which was supported in bias analysis. It is open whether competing risks of cause-specific death other than circulatory mortality reduce an effect of the number of teeth on all-cause mortality. An effect of denture use on circulatory mortality remains to be established, as well as whether the number of replaced teeth affects mortality. Specifying the role of potential pathways by which tooth loss-related mortality is mediated will possibly increase the value of dental treatment for general health.