- Objective. To analyze the factors associated with mortality in patients with systemic lupus erythematosus (SLE), followed prospectively in a single center. Methods. The study included 665 patients with SLE followed over a 20-year period according to a standard protocol. Clinical laboratory information has been entered into a database. Univariate analysis was carried out to identify prognostic factors of death. The Cox proportional hazard regression model was used to estimate risk ratio of death. Results. Renal damage, thrombocytopenia, lung involvement, systemic lupus erythematosus disease activity index (SLEDAI) ≥ 20 at presentation, and age ≥ 50 at diagnosis were predictive factors for mortality in the univariate as well as in the multivariate analyses. Hypertension and ischemic heart disease were significantly associated with death only in the univariate analysis. Conclusion. Renal damage, thrombocytopenia, SLEDAI ≥ 20 at presentation, lung involvement, and age ≥ 50 at diagnosis are prognostic factors associated with mortality.