Hemorrhagic cystitis (HC) has been reported with increased frequency following post-transplantation cyclophosphamide (PTCy)–based haploidentical hematopoietic cell transplantation (HCT) along with a strong association with BK viruria. We prospectively evaluated the incidence of BK viruria and HC in 115 patients (median age 20 years, 2–65) undergoing PTCy-based haploidentical HCT with ( n  = 71) or without ( n  = 44) CTLA4Ig. HC prophylaxis consisted of a continuous infusion of mesna 30 min prior and 48 h post-PTCy. The overall incidence of BK viruria was 65.7%. None with BK viruria < 10 4 copies/ml developed clinical symptoms ( n  = 65). The incidence of BK viruria ≥ 10 4 copies/ml was 7.1% ( n  = 8) and 75% developed HC. The incidence of HC was 5.4% at a median of 30 days. Both BK viruria ≥ 10 4 copies/ml and HC were strongly associated with acute GVHD ( p  < 0.001). A higher NRM was observed in those with BK viruria ≥ 10 4 copies/ml, related to GVHD and its complications (41.7% vs 12.6%, p  = 0.04). The incidences of acute GVHD, vis-à-vis, overall BK viruria, BK viruria ≥ 10 4 copies/ml, and HC, tended to be lower in patients receiving CTLA4Ig. Thus, extended infusional mesna, coupled with significant reduction in alloreactivity along with possible preservation of antiviral immunity associated with the use of CTLA4Ig, was probably responsible for a much lower incidence of BK viruria and resultant HC than reported previously following PTCy-based haploidentical HCT.