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Objectives: To examine changes in presence of methamphetamine in toxicology testing among outpatients receiving healthcare in Boston, Massachusetts., Methods: A serial cross-sectional study of oral fluid drug test results over a 6-year period of all patient specimens submitted for testing as part of routine care across an academic medical center in Boston, Massachusetts and affiliated primary care practices which has roughly 48,000 admissions and 500,000 primary care visits per year. All samples were subjected to definitive drug testing by liquid chromatography-tandem mass spectrometry for fentanyl, 6-monoacetylmorphine (6-MAM, metabolite of heroin), benzoylecgonine (metabolite of cocaine), cocaine, and methamphetamine. We compared positive rates and change over time across the same calendar months (February to July) of 6 consecutive years from 2014 to 2019., Results: Total of 17,303 oral fluid samples collected from outpatients receiving routine healthcare across 6 years were analyzed. Samples showing presence of methamphetamine, cocaine, and fentanyl increased over the study period, whereas 6-MAM presence decreased. From 2014 to 2019 samples with methamphetamine present increased from 0.9% to 5.1% and samples with 6-MAM present decreased from 9.5% to 2.8%. Fentanyl was added to the testing panel in 2017. In 2019, 15.7% of samples had fentanyl present. Polysubstance use was common; 44% of samples with methamphetamine also showed cocaine or benzoylecgonine, 25% showed fentanyl, and 3% showed 6-MAM presence., Conclusions: Presence of methamphetamine in oral fluid toxicology tests increased from 2014 to 2019 across a sample of outpatients receiving healthcare in Boston, Massachusetts. Regions of the country with high rates of opioid overdose may need to integrate harm reduction and addiction treatment resources for stimulant use disorder in addition to opioid use disorder., (Copyright © 2020 American Society of Addiction Medicine.)