Introduction: BK polyomavirus-associated hemorrhagic cystitis (BKPyV-HC) is a well-recognized infective complication of hematopoietic cell transplant (HCT) with increased organ dysfunction and mortality. This study was performed to describe the local incidence, risk factors, and outcomes of BKPyV infection. Methods: This retrospective case–control study was conducted between 2007 and 2016 from a tertiary hospital in South India. We identified HCT recipients diagnosed with BKPyV-HC and compared them with recipients over the same period who did not develop BK virus infection matched for age, sex, diagnosis, and donor type. We collected data from central electronic medical records and databases maintained in the departments of hematology and virology. Results: Over the study period, 1276 transplants were performed, of which 262 patients (20.5%) developed HC and 105 (8.2%) were BKPyV-positive. Grade 3 HC was most commonly (57.1%) seen, and the median time to develop BKPyV-HC was 35 (range 0–858) days. Survival was significantly lower in the cases (42.9% vs. 61%, P < 0.05). On univariate analysis, the protective effect of nonmyeloablative conditioning ( P = 0.04), residual disease at the time of transplant in malignant conditions ( P = 0.001), lower CD34 dose ( P = 0.006), presence of acute graft versus host disease (GVHD, P < 0.001), reactivation of cytomegalovirus infection ( P < 0.001), and presence of bacterial urinary tract infection (UTI) ( P < 0.001) were significant factors. Multivariate logistic regression confirmed the presence of acute GVHD ( P = 0.041), bacterial UTI ( P < 0.001), and residual disease ( P = 0.009) at HCT as significant risk factors for BKPyV-HC. Conclusions: Our study affirms the homogeneity of BKPyV-HC disease in low- and middle-income HCT settings with prior reports and the need for therapeutic strategies to reduce its resultant mortality.