Abstract Background The legalization of medicinal or recreational marijuana across many states in the United States and other countries has driven demand for cannabis, hemp, and related products. Objective In the absence of federal regulations to ensure the product quality and safety of these products, each state issues its own guidance and sets its own regulations. Like food and pharmaceuticals, cannabis testing should include the analysis of heavy metals, which may be toxic if ingested or inhaled. Methods Based on established methods for the preparation and multi-elemental analysis of plant materials, a range of cannabis and cannabis-related products were prepared for analysis using microwave-assisted acid digestion followed by testing with inductively coupled plasma-mass spectrometry (ICP-MS). The sample preparation procedure was validated by measuring arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in four plant-based certified reference materials (CRMs). Results The mean ICP-MS results for As, Cd, Hg, and Pb were in good agreement (85–110%) with the certified concentrations. The accuracy and precision of the ICP-MS method for the determination of As, Cd, Hg, and Pb, as well as other elements, were tested by spiking the various cannabis samples at different concentration levels and determining the spike recoveries. The spike recoveries for As, Cd, Hg, and Pb in all spiked samples met the AOAC Standard Method Performance Requirements (SMPR®) for Determination of Heavy Metals in a Variety of Cannabis and Cannabis-Derived Products (SMPR 2020.001) of 60–115% for low-level spike and 80–115% for mid- and high-level spikes. Conclusion Microwave-assisted acid digestion and ICP-MS are suitable for trace metal preparation and analysis of cannabis, as well as related products, as shown by the results of this method. The repeatability and recovery results for As, Cd, Hg, and Pb met the method requirement criteria in the AOAC SMPR 2020.001. This method can be used for all stages of production to ensure safety with respect to toxic metals. Highlights A wide range of cannabis and hemp samples, from raw materials to finished products, are within scope for analysis using the microwave-assisted acid digestion/ICP-MS method.