Introduction: Harmful usage of tobacco is a public health problem of global concern and, in many countries, the main risk factor for non-communicable diseases. Yet, in the Peruvian Amazon, the geographical region believed to be tobacco's historical birthplace, this plant is associated with a strikingly different usage and repute: Tobacco (especially Nicotiana rustica L.) in this area is described as a potent medicinal plant, used topically or via ingestion to treat a variety of health conditions. The goal of this transdisciplinary field study was to investigate clinical applications of the tobacco plant as per Amazonian medicine exemplified in the practice of a reputed Maestro Tabaquero, an Amazonian traditional healer whose medical specialization focuses on tobacco-based treatments. Methods: Using a transdisciplinary clinical approach, we conducted in-depth interviews with the tabaquero applying the systematizing expert interview method, in order to map modes of preparation and administration, indications, contraindications, effects, risks, adverse effects, and systemic aspects of tobacco-based remedies.