Therapeutic approaches in systemic lupus erythematosus (SLE) have evolved over the last few decades, but their impact on prevention of organ damage is unknown. The objective of this study was to compare new cumulative damage in SLE patients across different calendar periods. Patients from a large SLE cohort were divided into two subcohorts; the first diagnosed and followed between 1978 and 1988 (cohort #1, n=100) and the second between 1989 and 1999 (cohort #2, n=51). Initial Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) scores, and changes in scores over the observation intervals, were compared for the two groups. Logistic regression estimated adjusted odds ratios (OR) comparing damage accrual between the two cohorts. Medication exposures were noted. Baseline characteristics were similar between the two groups. At first assessment, the adjusted OR for a SLICC/ACR DI score > or =1 was 1.79 (95% CI 0.82, 3.88) for cohort #1 versus cohort #2. At the end of the observation interval, the adjusted OR for a SLICC/ACR DI score > or =1 was 1.22 (0.58, 2.55) for cohort #1 versus cohort #2. The adjusted OR for accruing damage over the observation interval in cohort #1 versus cohort #2 was 0.94 (0.39, 2.44). Increased medication exposure was evident for cohort #2 compared to cohort #1. Despite increased therapeutic measures used for patients in more recent periods, our data do not establish a clear difference in damage accrual. This emphasizes the need for strategies to effectively treat lupus-specific manifestations, while minimizing side effects and comorbidities.