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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Federico Wilhelm Agricola Foundation Objective. To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort.Methods. Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. the diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for 2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person-months of followup) were 3.85 (95% confidence interval [95% CI] 1.41-8.37), 2.7 (95% CI 1.41-4.76), and 0.54 (95% CI 0.37-0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18-4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39-0.99).Conclusion. Antimalarial drugs were shown to have a protective effect, possibly in a time-dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus. Hosp Prov Rosario, Rheumatol Serv, RA-2000 Rosario, Santa Fe, Argentina Univ São Paulo, Fac Med, Hosp Clin, São Paulo, Brazil Univ Nacl Rosario, RA-2000 Rosario, Santa Fe, Argentina Univ Antioquia, Medellin, Colombia Hosp Univ San Vicente de Paul, Medellin, Colombia Hosp Interzonal Gen Agudos Dr Oscar Alende, Mar Del Plata, Buenos Aires, Argentina Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil Hosp Univ Caracas, Caracas, Venezuela Hosp Salvador, Santiago, Chile Univ Chile, Santiago, Chile Hosp Escuela Eva Peron, Rosario, Santa Fe, Argentina Hosp Gen Occidente Secretaria Salud, Guadalajara, Jalisco, Mexico Hosp Nacl Guillermo Almenara Irigoyen, Lima, Peru Pontificia Univ Catolica Chile, Santiago, Chile Hosp Especialidades Ctr Med Nacl Siglo XXI, Inst Mexicano Seguro Social, Mexico City, DF, Mexico Hosp Privado, Ctr Med Cordoba, Cordoba, Argentina Inst Nacl Cardiol Ignacio Chavez, Mexico City, DF, Mexico Universidade Federal de São Paulo, São Paulo, Brazil Hosp Nacl Clin, Cordoba, Argentina Univ Alabama, Birmingham, W Midlands, England Universidade Federal de São Paulo, EPM, São Paulo, Brazil CNPq: 305468/2006-5 CNPq: 3031165/2008-1 Web of Science