Engraftment syndrome (ES) is increasingly observed in patients who receive auto-SCT. To investigate this fact, validate the clinical criteria for ES diagnosis and analyze the risk factors for this complication, we reviewed 328 consecutive peripheral blood auto-SCT performed during the past 7 years. A total of 43 patients presented with clinical or biological data suggestive of ES. Of the total, 41 (95%) and 22 (51%) could be diagnosed with ES using the Maiolino criteria (MC) and the Spitzer criteria (SC), respectively. The SC were less sensitive as they do not consider some relevant clinical data and limit the observation time after engraftment. All ES cases had high C-reactive protein (CRP) values not observed in the remaining patients at engraftment (median ± s.d.: 17.5 ± 7.3 vs 2.4 ± 3.4 mg per 100 ml; P ¼ 0.0001). Multivariate analysis showed a higher risk of ES in SCT performed in recent years (relative risk (RR) 2.3, 95% confidence interval (CI 1.0-4.7), female patients (RR 2.5, 95% CI 1.2-5.2), and absence of intensive chemotherapy before SCT (RR 8.8,). All patients except one improved after treatment with corticosteroids. The MC seem to be the best tool to establish a diagnosis of ES. In doubtful cases, the diagnosis could be confirmed by evaluating CRP. Auto-SCT in patients not receiving previous chemotherapy could explain the increasing incidence of ES in the past years.