Study Objectives: To investigate the effects of different doses of oral caffeine-paracetamol combinations in postdural puncture headache (PDPH) prophylaxis. Design: Prospective, randomized, placebo-controlled, blinded study. Setting: University hospital. Patients: A total of 210 ASA physical status I and II patients undergoing lower extremity surgery. Interventions: Patients were randomly divided into 3 groups. One hour before the spinal anesthesia, the first group (n = 70) received placebo, the second group (n = 70) received 500-mg paracetamol + 75-mg caffeine, and the third group (n = 70) received 500-mg paracetamol + 125-mg caffeine orally. The same doses were repeated every 6 hours for 3 days. Patients were then interviewed on days 1, 2, 3, 4, and 7 to inquire about any PDPH. The interviewer was unaware of the PDPH prophylaxis group members. Patients who were discharged early were interviewed by telephone. Measurements and Main Results: Postdural puncture headache occurred in 11 patients (15.7%) in group 1, 10 patients (%14.28) in group 2, and 10 patients (%14.28) in group 3. The differences between the groups were insignificant (P >.05). The complications due to spinal anesthesia were similar in the 3 groups. Side effects of caffeine such as lack of sleep, tachycardia, and hypertension were not observed in groups 2 or 3. Conclusions: Prophylactic administration of paracetamol-caffeine combinations at the stated doses does not prevent PDPH. (c) 2005 Elsevier Inc. All rights reserved.