Despite progress in management, patients with sickle cell disease who are experiencing acute painful episode are often incompletely treated. We compared meperidine and tramadol with respect to their effects on the hemodynamics and pain relief in patients with sickle cell disease who were admitted to the emergency department with painful crisis. A total of 68 patients with sickle cell disease were randomly assigned to receive either tramadol 1.5 mg/kg (n = 34) or meperidine 1 mg/kg (n = 34). Hemodynamic parameters were recorded at regular intervals after analgesic infusions. Pain intensity and relief were documented by visual analog and pain relief scale, respectively. Sedation level was defined according to Ramsay sedation scale. Both meperidine and tramadol administration resulted in a significant reduction in systolic and diastolic blood pressure after 2 hours (P < .05). Efficacy in pain relief between the analgesics was more rapid and better in the meperidine group, although the degree of relief were significantly improved compared to baseline levels in both groups (P < .05). Sedation was more commonly seen in the meperidine arm. None of the patients had experienced neurotoxicity. In summary, both agents had proven safe and effective for emergent use in patients with sickle cell disease. Avoiding meperidine injections as recommended with previous guidelines needs to be carefully reconsidered especially when low doses are mentioned. (C) 2010 Published by Elsevier Inc.