Introduction Cytokine release syndrome (CRS) associated with T-cell replete haplo-HSCT is characterized by fever and high levels of inflammatory cytokines with symptom onset occurring early after infusion. We report our analysis of CRS development after T cell-replete haplo-HSCT after using prophylactic dexamethasone. Objetive To evaluate the incidence of CRS with dexamethasone prophylaxis during an outpatient-based peripheral blood haplo-HSCT, factors associated to CRS and its impact on transplant outcomes. Methods Adults undergoing T-cell replete haplo-HSCT in our transplant center between 2016-2018 were included. CRS was graded using the criteria described by Lee et. al. Conditioning was performed with fludarabine 25 mg/m2/day (day -5 to -3), cyclophosphamide 350 mg/m2/day (day -5 to -3), and oral melphalan 50-100 mg/m2 (day -2 to -1). Graft-versus-host disease (GVHD) prophylaxis consisted of post-transplant cyclophosphamide (PTCy) 50 mg/kg (days +3 to +4) as well as mycophenolate and either cyclosporine or tacrolimus starting on day +5. Dexamethasone 8 mg IV was administered on day 0 to +2 as CRS prophylaxis. Results Forty two patients were included. The most common underlying diagnosis was acute leukemia (n=22, 52%). Conditioning was myeloablative (n=33, 79%) or reduced-intensity (n=9, 21%). Thirty patients (71.4%) developed CRS. CRS severity was grade 1/2 in n=28 (66.7%) and grade 3 in n=2 (4.8%). Median time to onset occurred on day +2 (0-4) and usually resolved after PTCy on day +5 (range, 1-11). CRS incidence was not associated with CD34+ cells infused, DRI/HCT-CI scores, or conditioning intensity. Time to neutrophil and platelet engraftment were similar regardless of CRS. Hospitalization was required in 36 cases (87%) while n=6 (13%) were followed in a fully-outpatient basis, including 2 patients with grade 1 CRS. Survival outcomes and GVHD were similar (Table 1) Conclusion CRS was common despite dexamethasone prophylaxis, and most were grade 1/2. None of the factors evaluated were associated to CRS and it did not influence outcomes. Completely ambulatory conduct of HSCT was limited by the development of CRS. New strategies are required to prevent CRS and hospitalizations associated with haplo-HSCT.