Background: Renal biopsy is the golden tool for the diagnosis of proliferative lupus nephritis (LN), the level of histological activity, and the risk of end-stage renal disease (ESRD). Objective: This study aimed to investigate the value of repeated renal biopsy in the follow-up of proliferative LN patients and to determine the predictors for re-biopsy and re-induction. Methods: A retrospective study made on 184 LN Egyptian females, data from 2002 to 2020 included history, examination, laboratory investigations, and results of repeated biopsies. Results: Remission was achieved in 46.7% of patients versus 53.3% with non-remission. The non-remission was significantly higher with higher chronicity index (CI), CYC 1ry induction, and AZA 1ry maintenance than with lower CI, MMF 1ry induction, or maintenance (S). About 41.8% of patients had a 2nd biopsy, and 30.9% received re induction therapy. Significant predictors for non-responding included type of 1ry induction and activity index (AI). In the CYC 1ry induction group, the AI mean±SD in 2nd biopsy (6.83 ±4.02) was significantly lower than in 1st biopsy (10.6 ±4.08) (S), while the CI mean±SD in 2nd biopsy (3.4 ±1.4) was significantly higher than in 1st biopsy (2.5 ±1.2) (S), with no significant difference in the MMF group. Out of the 184 LN patients who had their 1st biopsy, 77 patients (41.8%) had a 2nd biopsy, with no difference as regards the class of LN, but the AI mean±SD was significantly lower in the 2nd biopsy (7.4±4.2) compared to 1st biopsy (10.0±4.4) (S), while the CI mean±SD was higher in the 2nd biopsy (3.0±2.3) compared to the 1st biopsy (2.4±1.6) (S