The purpose of the study was analysis of leg alignment and tibial slope comparing intramedullary versus extramedullary tibial instrumentation in the Genesis II MIS-TKA (Smith & Nephew, Memphis, USA).A prospective randomized study was performed according to the CONSORT guidelines. All patients (56 patients) for MIS-TKA were included, if the pre-operative standing long leg X-ray demonstrated the tibia eligible for use of both intra- and extramedullary MIS tibial instrumentation. Randomization was performed by envelope selecting intra- or extramedullary tibia MIS instrumentation. All patients were operated by, or under supervision of, one experienced knee surgeon (RJ). Measurements of leg alignment and tibial slope were made on standardized long leg standing X-rays and lateral knee X-rays performed pre-operatively and 4–12months post-surgery. Leg alignment was defined as being within or outside the range of 3° varus–valgus on the mechanical leg. The tibial slope was compared pre- and post-surgery.In the present study, there was no difference in leg alignment after MIS-TKA comparing intramedullary versus extramedullary tibial instrumentation. Restoration of tibial slope was significantly better with use of the extramedullary tibial instrumentation.