People with schizophrenia die prematurely, yet regional differences are unclear. PRISMA 2020 -compliant systematic review/random-effects meta -analysis of cohort studies assessing mortality relative risk (RR) versus any control group, and moderators, in people with ICD/DSM-defined schizophrenia, comparing countries and continents. We conducted subgroup, meta -regression analyses, and quality assessment. The primary outcome was all -cause mortality. Secondary outcomes were suicide-, /natural -cause- and othercause -related mortality. We included 135 studies from Europe (n = 70), North -America (n = 29), Asia (n = 33), Oceania (n = 2), Africa (n = 1). In incident plus prevalent schizophrenia, differences across continents emerged for all -cause mortality (highest in Africa, RR=5.98, 95 %C.I.=4.09-8.74, k = 1, lowest in North -America, RR=2.14, 95 %C. I.=1.92-2.38, k = 16), suicide (highest in Oceania, RR=13.5, 95 %C.I.=10.08-18.07, k = 1, lowest in NorthAmerica, RR=4.4, 95 %C.I.=4.07-4.76, k = 6), but not for natural -cause mortality. Europe had the largest association between antipsychotics and lower all -cause mortality/suicide (Asia had the smallest or no significant association, respectively), without differences for natural -cause mortality. Higher country socio-demographic index significantly moderated larger suicide -related and smaller natural -cause -related mortality risk in incident schizophrenia, with reversed associations in prevalent schizophrenia. Antipsychotics had a larger/smaller protective association in incident/prevalent schizophrenia regarding all -cause mortality, and smaller protective association for suicide -related mortality in prevalent schizophrenia. Additional regional differences emerged in incident schizophrenia, across countries, and secondary outcomes. Significant regional differences emerged for all -cause, cause -specific and suicide -related mortality. Naturalcause death was homogeneously increased globally. Moderators differed across countries. Global initiatives are needed to improve physical health in people with schizophrenia, local studies to identify actionable moderators.