Early detection of polyomavirus BK (BKV) viremia and reduction of immunosuppression is recommended for preventing polyomavirus‐associated nephropathy (PyVAN), but systematic histological evaluations were not performed in previous studies. We routinely screen for decoy cells and, if positive, measure plasma BKV‐loads. In a cohort of 203 consecutive renal transplantations performed from 2005–2008, 38 patients (19%) developed BKV‐viremia and were treated with reduction of immunosuppression. Based on subsequent allograft biopsy results and peak BKV‐viremia, patients were assigned to three groups: (i) definitive PyVAN (n = 13), (ii) presumptive PyVAN defined by plasma BKV‐loads of ≥4 log10 copies/ml (n = 17) and (iii) low BKV‐viremia (n = 8). Clearance of BKV‐viremia was achieved in 35/38 patients (92%) and subsequent clinical rejection occurred in 3/35 patients (8.6%), both without any difference among the groups. Patients with definitive PyVAN had higher peak plasma BKV‐loads and required longer time for clearance (8.8 vs. 4.6 vs. 2.9 months; p = 0.001). However, allograft function remained stable from baseline to last follow‐up at 34 months (range 18–60) in all three groups with median serum creatinine of 1.6 mg/dl, 1.6 mg/dl and 1.3 mg/dl, respectively. We conclude that screening for BKV‐replication and reduction of immunosuppression is an effective strategy to preserve medium‐term allograft function even in patients developing definitive PyVAN.