With the continuous growth of air traffic flow, the hazard of aircraft encountering wake vortex at high altitude is increasing. To identify the hazard area of wake vortices and increase the capacity of upper airspace, in present work, the dissipation characteristics of the wake vortex at high altitude are analyzed. Considering the changes of flight attitude and trajectory after the aircraft enters the wake, a multi-parametric calculation method is used to study the severities of wake encounters. To determine the minimum acceptable safety level of wake encounters, the upset parameters of different aircraft-type combinations in lower airspace are calculated when the leading aircrafts are 43 typical models. Based on the multi-parametric calculation method, the safety separation of wake at high altitude is studied. Compared with those in medium and low altitudes, wake vortices in high altitudes have larger initial strengths and dissipation rates. When the leading aircraft is a super-heavy or heavy-sized aircraft, it is necessary to increase the safety separation of 1.1–2.1 km. Since the findings here are broadly applicable to assess the severity of high-altitude wake encounter, the approach provided can significantly enhance the safety of air traffic control in upper airspace.