By using a patient-controlled analgesia (PCA) delivery system, we compared the clinical advantages and disadvantages of PCA with tramadol and PCA with a mixture of tramadol plus lysine acetyl salicylate (a soluble aspirin). Fifty adult patients who had undergone major orthopedic surgeries were enrolled into a prospective, randomized, and double-blinded study. The general anesthesia was performed in a standard manner. At the beginning of wound closure, an equal volume dose of either tramadol 2.5 mg/kg (Group 1) or tramadol 1.25 mg/kg + lysine acetyl salicylate 12.5 mg/kg mixture (Group 2) was administered slowly IV. These solutions were continued postoperatively for IV PCA. Pain control, patient satisfaction, vital signs, and adverse effects were assessed for 48 h. Visual Analog Scale </=3 could be achieved with either group. Total tramadol consumption was significantly less in Group 2 than in Group 1 (614 +/- 259 mg vs 923 +/- 354 mg) (P: < 0.05). Patients in Group 2 were more alert (P: < 0.05). Blood loss from the surgical drain was similar, 865 +/- 275 mL (Group 1) vs 702 +/- 345 mL (Group 2). We conclude that aspirin can be used as an effective and safe adjuvant to tramadol for PCA after orthopedic surgery. CONCLUSIONS Injectable aspirin can be used as an effective and safe adjuvant to tramadol for patient-controlled analgesia (PCA) in orthopedic patients. The tramadol requirement is therefore reduced. This combination supports the concept that drugs other than opioids can be used for PCA.