PURPOSE Hemorrhagic cystitis (HC) is a frequent complication during allogeneic hematopoietic stem-cell transplantation (HSCT). HC worsen transplant outcomes and patients wellbeing in terms of pain, medicalization and need for supportive care. Deeper understanding of HC risk factors may contribute to focus on more intense prevention in high risk patients. METHODS In this report we analyzed 237 consecutive patients who had received HSCT in order to identify possible risk factors for HC and their consequences, focusing on transplant- and gender-related risk factors. RESULTS HC occurred in 17% of patients, with higher incidence in males (21% vs 11%, p = 0.03). Risk factors for HC were age over 55 years, recipients male gender, mismatched-HLA, reduced intensity conditioning and cyclophosphamide-based graft versus host disease (GVHD) prophylaxis. Patients with grade II-IV acute GVHD and detectable BKV and JCV viruria developed more HC. In multivariate analysis, higher age remained independent (p = 0.013). Patients with HC experienced longer hospitalization and higher non relapse mortality (NRM). Prostatic hyperplasia (more than 40 cm^3) was found in 33% of male patients, who developed HC in 32% of cases (vs 16% in patients with smaller prostates, p = 0.032). In male patients, prostatic volume and age were independent risk factors for HC (p = 0.016 both). CONCLUSIONS Age is the major risk factor for HC, with a possible role for cyclophosphamide based GVHD prophylaxis and HLA mismatch. In male population, prostatic hyperplasia is an independent additional risk. As HC is frequent and associates with prolonged hospitalization, more intensive prophylactic strategies could be considered in high-risk subsets.