Introduction: Primary care paramedics (PCPs) have limited options to provide analgesia during transport thus timely pain relief is often significantly delayed. Inhaled nitrous oxide is considered usual care for PCPs, but is limited in effectiveness. Intranasal (IN) ketamine has been shown to provide effective analgesia with no deleterious effects on cardiorespiratory function thus may provide rapid, easily-administered and well-tolerated analgesia in prehospital transports. Methods: This was a randomized double-blind pilot series. Patients with an acute painful condition reporting a pain score of 5 or more on an 11-point verbal numeric rating scale (VNRS) were included. Exclusion criteria were age under 18 years, known intolerance to ketamine, non-traumatic chest pain, altered mental status, pregnancy and nasal occlusion. Patients were randomized to 0.75 mg/kg of IN ketamine or IN saline. All patents received inhaled nitrous oxide. The primary outcome was the proportion of patients experiencing a reduction in VNRS pain score of two points or more (clinically significant pain reduction) at 30 minutes. Secondary outcomes were patient-reported comfort, patient and provider satisfaction, and incidence of adverse events. Results: 40 patients were enrolled, 20 in each group. 80% of IN ketamine patients compared to 60% of placebo patients reported a 2-point reduction in VNRS pain score by 30 minutes. 50% of ketamine vs 25% of placebo patients reported feeling moderately or much better. 85% of ketamine vs 75% of placebo patients reported any improvement in subjective comfort. 80% of ketamine patients reported minor adverse effects compared to 52% of placebo patients. No serious adverse effects were reported. Conclusion: The addition of IN ketamine to usual care with nitrous oxide appears to result in a greater proportion of patients reporting a clinically significant reduction in VNRS pain score and improved subjective comfort, with a greater incidence of minor adverse effects. These findings will be used to power a definitive randomized double-blind trial.