Abstract Background Several studies have compared the clinical features and outcomes of late- and early-onset systemic lupus erythematosus (SLE) patients. However, these previous studies were uncontrolled. The current study aimed to compare late- and early-onset SLE patients while controlling for sex and year at diagnosis (± 1 year). Methods The medical records of SLE patients in a lupus cohort from January 1994 to June 2020 were reviewed. Late-onset patients were identified as those with an age at diagnosis ≥ 50 years. The early-onset patients (age at diagnosis < 50 years) were matched by sex and year at diagnosis with the late-onset patients at a ratio of 2:1. Clinical manifestations, disease activity (mSLEDAI-2K), organ damage scores, treatment, and mortality were compared between the two groups. Results The study comprised 62 and 124 late- and early-onset patients, respectively, with a mean follow-up duration of 5 years. At disease onset, when comparing the early-onset patients with the late-onset patients, the latter group had a higher prevalence rate of serositis (37.0% vs. 14.5%, p < 0.001) and hemolytic anemia (50.0% vs. 33.9%, p = 0.034) but lower prevalence rate of malar rash (14.5% vs. 37.1%, p = 0.001), arthritis (41.9% vs. 62.1%, p = 0.009), leukopenia (32.3% vs. 50.0%, p = 0.022) and lymphopenia (50.0% vs. 66.1%, p = 0.034). The groups had similar SLE disease activity (7.41 vs. 7.50), but the late-onset group had higher organ damage scores (0.37 vs. 0.02, p < 0.001). The rates of treatment with corticosteroids, antimalarial drugs, or immunosuppressive drugs were not different. At their last visit, the late-onset patients still had the same pattern of clinically significant differences except for arthritis; additionally, the late-onset group had a lower rate of nephritis (53.2% vs. 74.2%, p = 0.008). They also had a lower level of disease activity (0.41 vs. 0.57, p = 0.006) and received fewer antimalarials (67.7% vs. 85.5%, p = 0.023) and immunosuppressive drugs (61.3% vs. 78.2%, p = 0.044), but they had higher organ damage scores (1.37 vs. 0.47, p < 0.001) and higher mortality rates/100-person year (3.2 vs. 1.1, p = 0.015). After adjusting for disease duration and baseline clinical variables, the late-onset patients only had lower rate of nephritis (p = 0.002), but still received fewer immunosuppressive drugs (p = 0.005) and had a higher mortality rate (p = 0.037). Conclusions In this sex- and year at diagnosis-matched controlled study, after adjusting for disease duration and baseline clinical variables, the late-onset SLE patients had less renal involvement and received less aggressive treatment, but had a higher mortality rate than the early-onset patients. late earlyonset early onset (SLE However uncontrolled ± ( year. . year) 199 202 reviewed Lateonset Late years lateonset 21. 21 2 1. 2:1 manifestations mSLEDAI2K, mSLEDAI2K mSLEDAIK mSLEDAI 2K , K (mSLEDAI-2K) 6 12 respectively followup follow up 37.0% 370 37 0 (37.0 vs 145 14 14.5% 0.001 0001 001 50.0% 500 (50.0 339 33 9 33.9% 0.034 0034 034 (14.5 371 37.1% 0.001, 41.9% 419 41 (41.9 621 62.1% 0.009, 0009 0.009 009 0.009) 32.3% 323 32 3 (32.3 0.022 0022 022 661 66 66.1% 0.034. 7.41 741 7 (7.4 7.50, 750 7.50 7.50) 0.37 037 (0.3 002 02 0.02 0.001. corticosteroids different visit additionally 53.2% 532 53 (53.2 742 74 74.2% 0.008. 0008 0.008 008 0.008) 0.41 041 (0.4 057 57 0.57 0.006 0006 006 67.7% 677 67 (67.7 855 85 85.5% 0.023 0023 023 61.3% 613 61 (61.3 782 78 78.2% 0.044, 0044 0.044 044 0.044) 1.37 137 (1.3 047 47 0.47 rates/100person rates100person ratesperson rates/100 person 100 3.2 (3. 11 1.1 0.015. 0015 0.015 015 0.015) variables 0.002, 0002 0.002 0.002) 0.005 0005 005 0.037. 0037 0.037 0.037) diagnosismatched 19 20 2: (mSLEDAI-2K 37.0 (37. 14.5 0.00 000 00 50.0 (50. 33.9 0.03 003 03 (14. 37.1 41.9 4 (41. 62.1 32.3 (32. 66.1 7.4 (7. 75 7.5 0.3 (0. 0.0 53.2 (53. 74.2 0.4 04 05 0.5 67.7 (67. 8 85.5 61.3 (61. 78.2 004 0.04 1.3 13 (1. 100person rates100 rates/10 10 3. (3 0.01 01 37. (37 14. 50. (50 33. (14 41. (41 62. 32. (32 66. 7. (7 0. (0 53. (53 74. 67. (67 85. 61. (61 78. (1 rates10 rates/1 (5 (4 (6 rates1 rates/