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Background: Patients who survive gunshot wounds often have retained missiles. Unlike intra-articular retained missiles, extra-articular retained missiles (EARMs) are not routinely removed. Cases of lead toxicity from EARMs have been described. This study seeks to determine whether blood lead levels are elevated in emergency department patients with EARMs compared with matched controls, whether clinical symptoms of lead toxicity are more prevalent in patients with EARMs than in controls, and whether longer missile retention times or recent hypermetabolic conditions are associated with higher blood lead levels., Methods: One hundred twenty adults with EARMs and 120 age- and gender-matched controls with no history of gunshot wound were prospectively enrolled on presentation to a large urban emergency department. Whole blood lead (WBL), zinc protoporphyrin, and hemoglobin levels were obtained. Patients completed a questionnaire regarding time since gunshot injury; symptoms of lead toxicity; and occurrence within 30 days of any surgery, alcohol abuse, illicit drug abuse, diabetic ketoacidosis, hyperthyroidism, infection, fracture, pregnancy, or lactation., Results: Five EARM patients (4%) and no control patients (0%) had WBL greater than our threshold for medical follow-up (20 microg/dL). Mean WBL was 6.71 microg/dL (95% confidence interval [CI], 5.68-7.74 microg/dL) in EARM patients and 3.16 mug/dL (95% CI, 2.79-3.53 microg/dL) in controls. This difference was statistically significant when analyzed by matched pairs t test (p = 0.0001). There was no difference in the number of symptoms associated with lead toxicity that were noted by EARM patients versus controls (p = 0.377). Longer duration of missile retention was not associated with higher blood lead levels (r = 0.125, p = 0.172). Of the five hypermetabolic conditions analyzed, only fractures were associated with elevated blood lead levels (9.95 microg/dL [95% CI, 5.77-14.13 microg/dL] in EARM patients with fractures vs. 6.23 microg/dL [95% CI, 5.23-7.23 microg/dL] in EARM patients without fractures)., Conclusion: Patients with EARMs have significantly elevated blood lead levels compared with matched controls. The occurrence of a bony fracture within the past 30 days is associated with a higher lead level. In 96% of patients with EARMs, elevated lead levels were not clinically significant and did not change patient management.