OBJECTIVE To determine if patient weight is predictive of the degree of analgesic response to morphine in opioid naïve patients in the emergency department (ED). DESIGN Prospective observational study. SETTING Academic, tertiary ED, designated as a level 1 trauma center. PATIENTS Fifty opioid naive adult patients who were administered a single fixed intravenous dose of 4 mg morphine on initial presentation to the ED. INTERVENTIONS Pain was assessed at baseline and then repeated at 15- and 30-minute postdose using an 11-point (0-10) verbal numerical rating scale (NRS). MAIN OUTCOME MEASURES The primary outcome was maximum analgesic response, which is defined as the difference between initial pain score and lowest pain score achieved postdose at 15 or 30 minutes. Linear regression was used to analyze the relationship between maximum pain reduction and patient weight. RESULTS Mean patient weight was 85.4 kg (standard deviation = +/- 24.2; range 47.6-170). Median initial pain score was 8 (range 6-10) and median lowest pain score achieved postdose was 4 (range 0-10). In the linear regression analysis, patient weight did not predict the degree of pain reduction on the NRS (coefficient = 0.002 [95% confidence interval (CI) = -0.029-0.032], R2 < 0.001, p = 0.91). The only variable predictive of the degree of pain reduction was initial pain score (coefficient = 0.537/95% CI = 0.013-1.0611, R2 = 0.081,p = 0.045). CONCLUSIONS Patient weight was not significantly associated with the degree of analgesic response to morphine in opioid naive adults. Morphine dosing based on patient weight alone is not necessary in adults in the ED.