To systematically review and meta-analyse the studies investigating the association between smokeless tobacco (SLT) use and all-cause mortality and cause-specific mortality outcomes among adult users of SLT and estimate the number of attributable deaths worldwide. Random-effects meta-analysis was used to estimate the pooled risk of death due to SLT use. Population attributable fractions were derived and used to calculate the number of attributable deaths. Observational studies published upto 2015 were identified through MEDLINE, IndMED, Google Scholar and other databases. Data on the prevalence of SLT use was obtained from latest reports or national surveys. Data on the disease burden were obtained from the Global Burden of Disease Study. Hospital-based or community-based case-control and cohort studies that adjusted for the smoking status were included. 16 studies that provided estimates for mortality due to all cause, all cancer, upper aerodigestive tract (UADT) cancer, stomach cancer, cervical cancer, ischaemic heart disease (IHD) and stroke were included. A significant association was found for mortality due to all cause (1.22; 1.11-1.34), all cancer (1.31; 1.16-1.47), UADT cancer (2.17; 1.47-3.22), stomach cancer (1.33; 1.12-1.59), cervical cancer (2.07; 1.64-2.61), IHD (1.10; 1.04-1.17) and stroke (1.37; 1.24-1.51). Subgroup analysis showed major regional differences. Globally, the number of attributable deaths from all-cause mortality was 652 494 (234 008-1 081 437), of which 88% was borne by the South-East Asian region. SLT is responsible for a large number of deaths worldwide with the South-East Asian region bearing a substantial share of the burden.