Pharmacokinetic studies have shown that oral transmucosal absorption of fentanyl is relatively rapid compared with gastrointestinal absorption, and it results in increased bioavailability. We designed this study to establish the relative potency of oral transmucosal fentanyl citrate (OTFC) compared with IV morphine in 133 postoperative patients. The morning after surgery, patients randomly received one dose of either OTFC (200 or 800 μg) and a placebo IV injection or IV morphine (2 or 10 mg) and an oral transmucosal placebo unit. Pain intensity, pain relief, time to meaningful pain relief, and time to remedication were recorded. Median time to onset of relief was approximately 5 min for all groups. Over the first hour, little difference among treatment groups was seen for pain intensity and pain relief. By 2 h after study drug administration, 800 μg of OTFC and 10 mg of IV morphine generally produced similar analgesia, which was better than the smaller doses. Duration of analgesia with the larger doses (800 μg of OTFC and 10 mg of morphine) was similar and longer that produced by the smaller doses. The larger doses of OTFC and morphine produced better and more sustained analgesia than 200 μg of OTFC or 2 mg of morphine. Implications: The relative potency of oral transmucosal fentanyl citrate (OTFC) to IV morphine was 8-14:1. In this postoperative setting, OTFC produced rapid pain relief similar to that produced by IV morphine. The larger doses of OTFC (800 μg) and morphine (10 mg) produced better and more sustained analgesia than 200 μg of OTFC or 2 mg of morphine.