Work at high altitude (elevation equal to or greater than 3000 m above sea level) results in a physiological adaptation of the human organism to changing environmental conditions. The main problem related to the altitude is represented by the reduction of partial pressure of oxygen (hypoxia). Our study takes into consideration occupational risk factors: those related to physical environment of high altitude; those related to the worker; those related to the characteristics of the job. It is finally addressed the decision making process related to the formulation of the judgment of suitability for performance of work activities at high altitude. The health protocol proposed requires an accurate anamnestic investigation aimed at gathering information on pre-existing pathophysiological conditions that need, once identified, clinical and instrumental tests specific and targeted. These clinical protocols are analyzed and proposed for the main pathophysiologic conditions that pose a risk to health at high altitude.