Our objective was to study the demographic, clinical, laboratory features, therapy, and outcome of systemic lupus erythematosus (SLE) patients. In this retrospective study, which covered a 27-year period (1980-2006), 624 SLE patients referring to King Khalid University hospital, Riyadh were included. There were 566 females and 58 males (9.8:1) with a mean age of 34.3 (range 8-71) years and mean age at disease onset of 25.3 years (range 0.08-67). The mean disease duration was 9.3 years (range 0.3-30). The most common disease manifestations were hematological abnormalities (82.7%), arthritis (80.4%), and mucocutaneous symptoms (64.3%). The prevalence of malar rash was 47.9%, discoid rash 17.6%, photosensitivity 30.6%, oral ulcers 39.1%, serositis 27.4%, nephritis 47.9%, and neuropsychiatric manifestations 27.6%. Lymphopenia (40.3%), anti-Ro (53.1%), anti-La (26.6%), anti-Sm (41.6%), anticardiolipin IgG (49.7%), and IgM (33.5%) antibodies were highly prevalent. Antinuclear antibodies were detected in 99.7% and anti-DNA in 80.1% patients. Low C3 and C4 were observed in 45.4% and 42.2%, respectively. Therapy included oral steroids (96.2%), IV cyclophosphamide (34.1%) and azathioprine (32.1%) along with other drugs. Long-term remission was achieved in 82.4%, disease was active in 2.6%, renal failure occurred in 4.3% requiring dialysis, 6.7% lost follow up and 4.0% patients died. Infections (48%) and active SLE (36%) were the common causes of death. The 5- and 10-year patient survival rate was 98% and 97%, respectively. This study suggests that, in our patients, SLE manifests with features similar to SLE patients from other Arab countries and Caucasia. In comparison to Caucasians, higher prevalence of anti-Ro antibodies is observed in our study, in some Middle-Eastern and Asian countries; this may likely be due to inter-ethnic variation owing to genetic differences. Our 5-year patient survival rate was similar to that of western countries, while 10-year survival rate was better than that of most places.