Background: Percutaneous renal biopsy (PRB) of native kidneys is an essential tool in the diagnosis and management of renal disease. We report one of the largest single-center experiences on the success and safety of the procedure. Methods: From June 1983 to March 2012, 1,055 adults underwent PRB using real-time ultrasound guidance and 14-gauge biopsy needles. Data were collected prospectively for 826 biopsies (78%). Statistical analysis was performed using the Mann-Whitney test, Wilcoxon matched pairs test and Kruskal-Wallis test for continuous data or the Fisher's exact test and χ² test for categorical data. Multivariate analysis using logistic regression was performed to determine which feature at baseline was predictive of a complication following renal biopsy. Results: Patients were aged 46 ± 17 years; 38% were male, 40% were white and 43% were African-American. Serum creatinine (SCr) was 2.3 ± 2.3 mg/dl (>1.5 mg/dl in 47%). The pre-PRB hemoglobin was 12 ± 2 g/dl (<11.0 g/dl in 35%). Adequate tissue for diagnosis was obtained in 99% of biopsies. Minor complications occurred in 8.1% of biopsies (mainly gross hematuria, in 4.5%). Major complications occurred in 6.6% of biopsies, with transfusions required in 5.3%. Only 1 death (0.09%) resulted from post-PRB bleeding. By multivariate analysis, baseline features predictive of a complication were systolic blood pressure >170 mm Hg (OR 4.2, 95% CI 1.8-9.8), bleeding time >7.5 min (OR 1.7, CI 1.2-2.5) and SCr >3.5 mg/dl (OR 1.8, CI 1.2-2.9). Conclusions: PRB of native kidneys using real-time ultrasound with a 14-gauge automated needle remains a successful and safe procedure.