Coffee consumption has been shown to be associated with various health outcomes, but no comprehensive review and meta-analysis of the association between coffee consumption and total mortality has been conducted. To quantitatively assess this association, we conducted a meta-analysis of prospective cohort studies. Eligible studies were identified by searching the PubMed and EMBASE databases for all articles published through June 2013 and reviewing the reference lists of the retrieved articles. Pooled relative risks (RR) with 95% CI were calculated using a random-effects model. We identified twenty studies of coffee consumption and total mortality, including 129,538 cases of deaths among the 973,904 participants. The RR of total mortality for the high v. low category of coffee consumption was 0.86 (95% CI 0.80, 0.92). The pooled RR for studies using ≥ 2-4 cups/d as a cut-off for the high category was similar to that for studies using ≥ 5-9 cups/d as the cut-off. By geographical region, the inverse association tended to be stronger for the eight studies conducted in Europe (RR 0.78, 95% CI 0.70, 0.88) and three studies carried out in Japan (RR 0.82, 95% CI 0.73, 0.92) than for the nine studies conducted in the USA (RR 0.92, 95% CI 0.84, 1.00). The inverse association was similar for men (RR 0.81, 95% CI 0.73, 0.90) and women (RR 0.84, 95% CI 0.79, 0.89). A weak, but significant, inverse association was found with moderate coffee consumption (1-2 cups/d; RR 0.92, 95% CI 0.87, 0.98). High decaffeinated coffee consumption was also found to be associated with a lower risk of death, but the data are limited. Our findings indicate that coffee consumption is associated with a reduced risk of total mortality.