To investigate demographic, clinical, laboratory, and immunological characteristics of patients with systemic lupus erythematosus (SLE) in southeastern areas of South Korea, and to perform survival analysis. We retrospectively evaluated 413 patients with SLE diagnosed in 3 tertiary rheumatology centers in South Korea from 1992 to 2016 by reviewing their medical charts. All patients fulfilled the 1997 revised American College of Rheumatology classification criteria for SLE. Most patients were women (92%), and the mean (±standard deviation) age at diagnosis was 30.9 (±12.9) years. The most common clinical manifestation was leukopenia (74.3%), followed by lymphopenia (73.6%), arthritis (59.1%), malar rash (48.4%), thrombocytopenia (46.5%), oral ulcer (35.1%), and biopsy-proven lupus nephritis (31.2%). Anti-nuclear, anti-double-stranded DNA, anti-Smith, and anti-Ro antibodies were positive in 97.8%, 70.1%, 38.4%, and 63% of patients, respectively. Twenty (4.8%) patients died during a median follow-up of 83months, and the cumulative 5-year and 10-year survival rates were 96.9% and 95.5%, respectively. The major causes of death were infection (50%) and lupus flare-up (50%). Male (hazards ratio [HR]=7.19, P=.001), pleuritis and/or pericarditis (HR=3.28, P=.012), childhood-onset (HR=3.57, P=.012), and late-onset (HR=4.65, P=.011) were independent risk factors for death. Compared with SLE cohorts in other ethnicities or countries, our patients tended to have a higher frequency of anti-Ro antibodies and hematologic disorders. This study describes clinical features of SLE in South Korea and suggests a remarkable phenotypic heterogeneity of SLE.