Preengraftment syndrome (PES) is a known complication following unrelated cord blood transplant (CBT) that has not been well characterized. We sought to determine the incidence and clinical outcome of PES among 326 patients <18 years of age who were prospectively enrolled on a multicenter CBT trial. All patients received a myeloablative (MA) transplant and a single cord blood unit (CBU). PES developed in 20% of the patients at a median of 10 days (range: 5-24). Patients receiving a CBU with a total nucleated cell (TNC) count of >5 x 10(7)/kg had significantly higher risk of developing PES (P = .02). There were significantly higher rates of grade II-V (P < .001), grade III-IV (P < .001) acute and chronic (P = .002) graft-versus-host disease (aGVHD, cGVHD) in those who developed PES. In a multivariate analysis, PES did not significantly affect overall survival (OS) (P = .38). We conclude that PES is common following CB transplant (CBT) and additional more intensive immune suppression might be considered to decrease the risk of developing aGVHD and cGVHD.