Post-dural puncture headache (PDPH) is a common complication of lumbar puncture. As invasice treatments for PDPH have known complications, pharmacologic management may be preferable. The aim of this study was to evaluate and to compare the efficacy of intravenous theophylline treatment of PDPH, in comparison with a placebo. We found that intravenous theophylline infusion was effective for decreasing the painfulness of PDPH compared with the control group. The mean visual analogue scale (VAS) value was 7.05 +/- 1.47 before the theophylline infusion and 2.88 +/- 2.31 after infusion. An average of 59.1% relief of pain was obtained in the group treated with theophylline infusion. The improvement in VAS in the study group was significant (p < 0.001), whereas that in the control group was not (p=0.15). The mean VAS decrease after theophylline infusion was 4.17 +/- 2.03 in the study group and 0.41 +/- 0.71 in the control group; the diffrence in improvement between the groups was significant (p < 0.01). Intravenous theophylline infusion is an easy, rapid, minimally invasive, an effective treatment for PDPH. It may be attempted in PDPH patients before invasive techniques are used. To the best of our knowledge, this is the first report on the effect of intravenous infusion of theophylline compared with a placebo in the treatment of PDPH. (c) 2007 Elsevier Ltd. All rights reserved.