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Background: This study investigates the impact of methamphetamine use on trauma patient outcomes. Methods: This retrospective study analyzed patients between 18 and 55 years old presenting to a single trauma center in San Bernardino County, CA who sustained traumatic injury during the 10-year study period (January 1st, 2005 to December 31st, 2015). Routine serum ethanol levels and urine drug screens (UDS) were completed on all trauma patients. Exclusion criteria included patients with an elevated serum ethanol level (> 0 mg/dL). Those who screened positive on UDS for only methamphetamine and negative for cocaine and cannabis (MA(+)) were compared to those with a triple negative UDS for methamphetamine, cocaine, and cannabis (MA(−)). The primary outcome studied was the impact of a methamphetamine positive drug screen on hospital mortality. Secondary outcomes included length of stay (LOS), heart rate, systolic and diastolic blood pressure (SBP and DBP, respectively), and total amount of blood products utilized during hospitalization. To analyze the effect of methamphetamine, age, gender, injury severity score, and mechanism of injury (blunt vs. penetrating) were matched between MA(−) and MA(+) through a propensity matching algorithm. Results: After exclusion, 2538 patients were included in the final analysis; 449 were patients in the MA(+) group and 2089 patients in the MA(−) group. A selection of 449 MA(−) patients were matched with the MA(+) group based on age, gender, injury severity score, and mechanism of injury. This led to a final sample size of 898 patients with 449 patients in each group. No statistically significant change was observed in hospital mortality. Notably, a methamphetamine positive drug screen was associated with a longer LOS (median of 4 vs. 3 days in MA(+) and MA(−), respectively, p < 0.0001), an increased heart rate at the scene (103 vs. 94 bpm for MA(+) and MA(−), respectively, p = 0.0016), and an increased heart rate upon arrival to the trauma center (100 vs. 94 bpm for MA(+) and MA(−), respectively, p < 0.0001). Moreover, the MA(+) group had decreased SBP at the scene compared to the MA(−) group (127 vs. 132 bpm for MA(+) and MA(−), respectively, p = 0.0149), but SBP was no longer statistically different when patients arrived at the trauma center (p = 0.3823). There was no significant difference in DBP or in blood products used. Conclusion: Methamphetamine positive drug screens in trauma patients were not associated with an increase in hospital mortality; however, a methamphetamine positive drug screen was associated with a longer LOS and an increased heart rate. [ABSTRACT FROM AUTHOR]