MXenes are two-dimensional metal carbides with promising applications in energy storage and sensors. Guidelines for safe, scalable MXene synthesis are important due to ongoing efforts to scale-up production of these novel nanomaterials. Hazard identification before scale-up will allow for inherently safer designs prior to actual implementation. Here, we investigate hazards associated with MXene production, including MAX phase synthesis from raw materials, etching of the MAX phase to MXene clay, exfoliation to MXene nanosheets, and postprocessing of MXenes with Ti3C2Tx as a model species. The major hazards in MXene synthesis are the potential for dust ignition, runaway reactions, and toxic chemical exposure. Because the synthesis of MXenes is a multistep process, safety guidelines for each step are evaluated, including preventive and mitigating measures, best practices, and emergency procedures and responses. This includes handling of combustible powders, exothermic reactions, and harsh chemical etchants. This study is intended to facilitate safer MXene synthesis across various levels of scale-up, from large laboratory batches to commercial production.