The objective was to determine whether an inhaled 50:50 mixture of nitrous oxide and oxygen (N(2)O/O(2)) provides significant pain and anxiety relief during intravenous cannulation in healthy adults. The study was conducted at the ED of a military teaching hospital. Participants included adult volunteers aged 18 to 50 years. Excluded were those with allergy to N(2)O, anemia, cardiac disease, pregnancy, asthma, or bone marrow disorder. A prospective, randomized, double-blind, placebo-controlled crossover design was used comparing a 50:50 mixture of N(2)O/O(2) versus O(2). After recording baseline nonhatched 100mm visual analog scales (VAS) for pain and anxiety, subjects inhaled gas 1 for 120 seconds, followed by antecubital intravenous cannulation, discontinuance of gas and VAS rating of procedural pain and anxiety. After 15 minutes, the experiment was repeated with gas 2. Ten subjects would detect a 12mm difference in pain or anxiety with a standard deviation of 10 mm, an alpha error under 0.05 and a power over 80%. Differences between VAS were compared by matched 2-tailed t-test. Eleven subjects were enrolled. One withdrew because of dizziness while inhaling gas (N(2)O). The 10 remaining subjects reported significantly less pain (N(2)O/O(2) 14.5mm, SD 18; O(2) 34.3mm, SD 23.4; P < .01) and anxiety (N(2)O/O(2) - 7.9mm, SD 7.8; O(2) 6.0mm, SD 11.6; P < .02) when inhaling N(2)O/O(2) than when inhaling O(2) alone. N(2)O/O(2) provided significant pain and anxiety reductions during intravenous cannulation. Some patients may experience adverse perceptions while using N(2)O, limiting its utility. Further studies defining the role of N(2)O as an anxiolytic agent, efficacy in actual patients, and cost comparisons with intravenous conscious analgesia/sedation, are warranted.