As Unmanned Aerial Systems’ (UAS) operations have increased for both military and civil purposes, UAS have started performing operations over populated areas as well as sharing the airspace with manned aircrafts. For the safety of manned aircraft crew and of people on the ground, the safety assessments of UAS are a vital issue. Safety analyses of UAS become increasingly challenging with newly introduced systems due to their high complexity and intelligent nature. Current system safety processes, however, are mainly based on conventional aircraft and therefore are not fully applicable to UAS. Different approaches and methods can be applied during the safety analysis of UAS design process, according to the operational areas of the UAS. This paper highlights system safety analysis process implemented during the design phase of a Medium Altitude Long Endurance (MALE) UAS. Modifications to the existing methodologies are introduced hereby.