The aim of this study was to determine the association between lupus autoantibodies and the clinical manifestations and outcome in a cohort of Puerto Ricans patients with systemic lupus erythematosus (SLE). All patients fulfilled the American College of Rheumatology classification criteria for SLE. Demographic parameters, clinical manifestations over time and damage accrual were obtained at the last study visit. Disease damage was assessed with the Systemic Lupus International Collaborating Clinics Damage Index (SDI). ANA, ANA pattern, and anti-dsDNA, anti-Smith, anti-Ro (SSA), anti-La (SSB) and anti-snRNP antibodies were measured at the time of SLE diagnosis. Chi-square test, Fisher exact test, ANOVA, logistic regression and general lineal model analyses were used to evaluate these associations. Ninety-six percent of patients were females. The cohort had a mean age of 40.2 +/- 12.0 years and mean disease duration of 9.6 +/- 7.0 years. Patients with elevated anti-dsDNA antibodies were more likely to have vasculitis, pericardial effusion, renal involvement, anaemia, leukopenia, lymphopenia and thrombocytopenia. Anti-Smith antibodies were positively associated with skin ulcerations, elevated liver enzymes, renal involvement and thrombocytopenia. Anti-Ro antibodies were related with the presence of discoid lupus, serositis, pneumonitis, elevated liver enzymes, hemolytic anaemia, leukopenia and lymphopenia. No positive associations were found for anti-snRNP or anti-La antibodies. The presence of anti-dsDNA, anti-Smith and anti-Ro antibodies was associated with higher SDI scores. In conclusion, anti-dsDNA, anti-Smith and anti-Ro antibodies are associated with several clinical manifestations and more damage accrual in Puerto Ricans with SLE. These findings provide valuable clinical and prognostic information for this ethnic population.