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Purpose: The study's aim was to assess whether polyomavirus DNAemia screening was associated with different outcomes in patients with positive viremia compared with negative viremia. Methods: Case‐control retrospective study of patients with polyomavirus DNAemia (viremia > 1000 copies/mL) matched 1:1 with controls. Control group consists of the patient who received a transplant immediately before or after each identified case and did have nil viremia. Finding: Ultimately, 120 cases of BK polyomavirus (BKPyV) were detected and matched with 130 controls. Of these, 54 were adult kidney transplant recipients (KTRs), 43 were pediatric KTRs, and 23 were undergoing hemato‐oncologic therapy, of which 20 were undergoing hematopoietic stem cell transplantation. The odds ratio (OR) for overall risk of poorer outcomes in cases versus controls was 16.07 (95% CI: 5.55‐46.54). The unfavorable outcome of switching the immunosuppressive drug (ISD) (14/40,35%) was no different from that of those treated with reduced ISD doses (31/71, 43.6%, P =.250). Acute rejection or graft‐versus‐host disease, previous transplant, and intensity of immunosuppression (4 ISDs plus induction or conditioning) were risk factors for BKPyV‐DNAemia (OR: 13.96, 95% CI: 11.25‐15.18, P <.001; OR: 6.14, 95% CI: 3.91‐8.80, P <.001; OR: 5.53, 95% CI: 3.37‐7.30, P <.001, respectively). Conclusions: Despite viremia screening, dose reduction, and change in therapeutic protocol, patients with positive BKPyV‐DNAemia present poorer outcomes and unfavorable results. [ABSTRACT FROM AUTHOR]