Introduction The objective was to systematically review studies reporting on health outcomes from smokeless tobacco (SLT) products. Methods We included published literature on the health impact of SLT from 01/01/2015 until 01/02/2020 following the PRISMA protocol using PubMed, Embase, Scopus and Google Scholar. Results Of 321 studies identified, 53 met eligibility criteria; 23(43%) were rated as poor, 21(39%) fair and 9(17%) as good. Health outcomes differed starkly between SLT products and global regions. SLT products in Asia, Middle East and Africa were associated with higher mortality (overall, cancer, CHD, respiratory but not CVD), and morbidity (CVD, oral and head and neck cancers), with odds ratios as high as 39 (shammah use). European studies showed no excess mortality (overall, CVD, from cancers) or morbidity (IHD, stroke, oral, head and neck, pancreatic or colon cancers) from several meta-analyses but single studies reporting elevated risk of rectal cancer and respiratory disorders. Pooled studies showed a protective effect against developing Parkinson’s disease. US studies showed mixed results for mortality (raised overall, CHD, cancer and smoking-related cancer mortality; no excess risk of respiratory or CVD mortality). Morbidity outcomes were also mixed, with some evidence of increased IHD, stroke and cancer risk (oral, head and neck). No studies reported on the health impact of switching from cigarettes to SLT products. Conclusion Our review has demonstrated stark differences between different SLT products in different regions on health impact, ranging from no harm from European snus to greatly increased health risks from SLT products used in Asia, Middle East and Africa. The literature on the impact of SLT products for harm reduction is incomplete and potentially misinforming policy and regulation.