Objectives <p>Renal transplant biopsy remains the gold standard for etiological diagnosis of graft dysfunction and subsequent management. When percutaneous renal biopsy (PRB) is contraindicated due to bleeding risk or limited percutaneous access, the fluoroscopy-guided transvenous femoral renal transplant biopsy (TFRB) might be a valuable alternative. This study aims to describe the TFRB technique, its safety, and efficacy.</p> Methods <p>All patients who underwent TFRB at our institution between 2020 and 2023 were retrospectively analyzed. Procedure outcomes, patients’ characteristics and follow-up data were collected. Adverse events were graded using the Adverse Events Classification of the Society of Interventional Radiology.</p> Results <p>From January 2020 to December 2023, 109 patients (median age 61.2&#xa0;years (Interquartile range (IQR), 54.5–68.6) ; 49 males (45.0%)) underwent 122 TFRB. Transvenous approach was indicated due to high bleeding risk in 61.5% (75/122), limited percutaneous access in 13.9% (17/122), or previous failed PRB in 2.5% (3/122). Biopsy success rate was 94.3%, with 7 graft vein catheterization failures. Adequate Banff 97 criteria specimens were obtained in 68.7% of cases, and a definitive histological diagnosis was achieved in 96.5% of biopsies. Complications occurred in 20.0% of procedures (23/115), including 9 major complications (7.8%), with no significant difference according to the TFRB indication (bleeding risk versus percutaneous limited access) (<i>p</i> = 0.70), use of antiplatelet agents (<i>p</i> = 0.24) or anticoagulants (<i>p</i> = 1.00).</p> Conclusion <p>This is the first large cohort study to demonstrates TFRB to be effective and safe in case of contraindication to PRB, providing valuable insights for graft dysfunction management.</p> Graphic abstract <p></p>