Objective The aim of the study was to investigate the association between sense of coherence (SOC) and all-cause mortality in the general adult population. Methods We conducted a systematic review and meta-analysis of prospective cohort studies. We searched eight electronic bibliographic databases for eligible studies. A random effects model and the restricted maximum likelihood method were used to calculate the pooled effect size. Results Eight studies were eligible for the meta-analysis. The studies included 48,138 participants, of whom 5307 died during a median follow-up of 14.1 years (range, 8–29.5 years). Their age ranged from 20 to 80 years, and 53% of them were men. In the meta-analysis model of crude values, the risk of all-cause mortality for individuals with a weak SOC (lowest tertile) was 1.30 (95% confidence interval [CI] = 1.09–1.55, p = .003, I 2 = 78.84%) compared with individuals with a strong SOC (highest tertile). In the model adjusted for age, the risk remained almost the same (risk ratio = 1.26, 95% CI = 1.15–1.38, p < .001, I 2 = 69.59%). In the model adjusted for several other risk factors for mortality, the risk was still 1.17 (95% CI = 1.07–1.27, p < .001, I 2 = 57.85%). Conclusions This meta-analysis shows that a weak SOC is associated with an increased risk of all-cause mortality in the general adult population. Future studies are needed to further develop assessment tools for SOC with good psychometric properties and to determine the disease processes that mediate the association of SOC with mortality.