BACKGROUND: There are currently no studies assessing effectiveness of sub-dissociative intranasal (IN) ketamine as the initial analgesic for adult patients in the ED. OBJECTIVE: The study aims to examine the effectiveness of sub-dissociative IN ketamine as a primary analgesic agent for adult patients in the ED. METHOD: This is a prospective, observational study of adult ED patients presenting with severe pain (>/=6 on 11-point scale at triage). IN ketamine dose was 0.7 mg/kg, with secondary dose of 0.5 mg/kg at 15 min if pain did not improve. After 6 months, initial dose was increased to 1.0 mg/kg with the same optional secondary dose. PRIMARY OUTCOMES: The primary outcomes are change in VAS rating at 30 min; percentage of patients reporting clinically significant reduction in VAS (>/=20 mm) at 30 min; dose resulting in clinically significant pain reduction. RESULTS: Of the 72 patients available for analysis, median age was 34.5 years and 64 were men. Median initial VAS rating was 76 mm (interquartile range [IQR]: 65-82). Median total dose of IN ketamine for all patients was 0.98 mg/kg (IQR: 0.75-1.15, range: 0.59-1.57). Median reduction in VAS rating at 30 min was 24 mm (IQR: 2-45). Forty (56 , 95 CI: 44.0-66.7) reported VAS reduction >/=20 mm, these patients having had a total median ketamine dose of 0.94 mg/kg (IQR: 0.72-1.04). CONCLUSION: IN ketamine, at a dose of about 1 mg/kg, was an effective analgesic agent in 56 of study patients. The place of IN ketamine in analgesic guidelines for adults requires further investigation.