Background: Acute kidney disease (AKD) is a recent definition reflecting ongoing physiopathological processes of an acute renal injury (AKI). Information on AKD in hematopoietic stem cell transplant (HSCT) is scarce and there is no available data on long-term outcomes. We aimed to determine the cumulative incidence of AKD in the first 100 days after HSCT; to identify risk factors for AKD in HSCT; and to determine the impact of AKD in 3-year overall survival and relapse-free survival in HSCT. Methods: A retrospective cohort study was conducted, considering AKD when AKI was present and the patient continued to meet the KDIGO criteria (creatinine and/or urinary output criteria) for 7 days or more. Survival analysis methods considering competing events were used for risk factors and disease-free survival, Cox proportional regression for overall survival, and stepwise regression methods for multivariable models. Results: We enrolled 422 patients. AKD incidence was 22.9% (95% CI: 19.2–27.4%). Higher body mass index (HR: 1.05, 95% CI 1.01–1.10; p = 0.034), HCT-CI score ≥ 2 (HR: 1.83, 95% CI 1.11–3.13; p = 0.027), allogeneic transplantation (HR:2.03, 95% CI 1.26–3.33; p = 0.004), higher C-reactive protein (HR:1.01, 95% CI 1.01–1.02; p < 0.001), and exposure to nephrotoxic drugs (HR: 4.81, 95% CI 1.54–4.95; p = 0.038) were independently associated with AKD. AKD had a significant impact on overall survival (HR: 1.75; 95% CI 1.27–2.39; p = 0.001). Conclusion: An awareness of the risk factors for AKD allows the identification of high-risk patients, enabling the timely implementation of preventive measures to alleviate the progression and impact of the disease.