Prophylactic epidural morphine administration after unintentional dural puncture with a large-bore needle has been shown to decrease the incidence of post-dural puncture headache. The authors hypothesized that prophylactic administration of intrathecal morphine would decrease the incidence of post-dural puncture headache and/or need for epidural blood patch after unintentional dural puncture.Parturients with an intrathecal catheter in situ after unintentional dural puncture with a 17-g Tuohy needle during intended epidural catheter placement for labor analgesia were enrolled in this randomized, double-blind trial. After delivery, subjects were randomized to receive intrathecal morphine 150 µg or normal saline. The primary outcome was the incidence of post-dural puncture headache. Secondary outcomes included onset, duration, and severity of post-dural puncture headache, the presence of cranial nerve symptoms and the type of treatment the patient received.Sixty-one women were included in the study. The incidence of post-dural puncture headache was 21 of 27 (78%) in the intrathecal morphine group and 27 of 34 (79%) in the intrathecal saline group (difference, -1%; 95% CI, -25% to 24%). There were no differences between groups in the onset, duration, or severity of headache, or presence of cranial nerve symptoms. Epidural blood patch was administered to 10 of 27 (37%) of subjects in the intrathecal morphine and 11 of 21 (52%) of the intrathecal saline group (difference 15%; 95% CI, -18% to 48%).The present findings suggest that a single prophylactic intrathecal morphine dose of 150 µg administered shortly after delivery does not decrease the incidence or severity of post-dural puncture headache after unintentional dural puncture. This study does not support the clinical usefulness of prophylactic intrathecal morphine after an unintentional dural puncture. : WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Epidural morphine has been suggested to be effective for preventing post-dural puncture headache, but the effects of intrathecal morphine in reducing the incidence of this complication is unknown WHAT THIS ARTICLE TELLS US THAT IS NEW: In a single-center, randomized, double-blind study, there was no evidence that intrathecal morphine prevented post-dural puncture headache.