The benefits of advanced hydraulic microprocessor controlled knee (MPK) joints have been well established and repeatedly confirmed. The Genium knee was introduced in 2011 containing an enhanced control concept including additional sensors and improved algorithms enabling a range of new functions for transfemoral amputees (TFAs). A systematic review was conducted to evaluate the effect of the Genium knee on ambulation, mobility, activities of daily living (ADLs) and quality of life compared to standard MPKs. The review was conducted according to PRISMA Guidelines and Recommendations of the State-of-Science Evidence Report Guidelines of the American Academy of Orthotists & Prosthetists. Twelve articles were included in the review and reported primarily on active subjects (MFCL-3/4) transitioning from C-Leg to Genium knee systems. The overall validity of the evidence was medium to high with the exception of one article having low validity. Synthesis of biomechanical analyses concludes that gait during level walking, stairs and ramps is more physiological and symmetric following accommodation and use of the Genium in community ambulating TFAs. Further, sound side loading and compensatory motions are reduced. Transitioning from C-Leg to the Genium knee additionally resulted in significant improvements in mobility, quality of life and the performance in activities of daily living (ADLs). A high level of evidence was identified when assessing the ability of Genium to improve gait quality and safety and performance in ADLs. While individual studies report significant improvements in terms of quality of life and mobility, additional studies are needed to increase the evidence level.Implications for rehabilitationMicroprocessor controlled prosthetic knees (MPKs) are well-established devices to serve patients with transfemoral amputation. Studies conducted mostly with the C-Leg MPK show that such knees significantly increase patient safety, ambulation, mobility, performance in activities of daily living and quality of life.Genium MPK includes advanced features which enable a range of new functions and functional benefits to patients. Transitioning from conventional MPKs (i.e., C-Leg) to Genium MPK resulted in more physiological gait, more equally distributed loading between the prosthetic and sound limbs, as well as reduced compensatory movements on the sounds side. These outcomes could potentially reduce the long-term risks of secondary physical complications in prosthetic users (i.e., osteoarthritis, osteoporosis). Genium significantly improved mobility, performance in activities of daily living, and quality of life in the patients using a conventional MPK (C-Leg).Different functioning principles of the MPKs presently available are responsible for different performance levels the knees offer to users. The amount of clinical evidence is also knee-dependent, with the C-Leg knee being most extensively tested in clinical studies. This systematic review concludes that Genium offers further advantages to transfemoral patients as compared to conventional MPKs (C-Leg).