Background and Objectives: Knee osteoarthritis (OA) is a frequent cause of pain, functional limitations, and a common reason for surgical treatment, such as joint replacement. Conservative therapies can reduce pain and improve function; thus, delaying or even preventing surgical intervention. Various individual conservative therapies show benefits, but combination therapies remain underexplored. The aim of this prospective case-study was to assess the effect of a conservative combination therapy in patients with painful varus knee OA. Materials and Methods: With strong inclusion and exclusion criteria, nine patients with painful varus knee OA (mean age 56 years (range 51−63 years) were selected and monitored over six months, using the following clinical outcome scores: pain visual analog scale (VAS), Western Ontario and McMaster Universities osteoarthritis index (WOMAC score), short-form−36 items (SF-36) quality of life score, and the sports frequency score. All patients received a standardized conservative trio-therapy with varus-reducing hindfoot shoe-insoles with a lateral hindfoot wedge, oral viscosupplementation, and physiotherapy for six months. Results: The pain was reduced significantly from initial VAS values of 5.4 points (range, 3−10) to values of 0.6 points (range, 0−3; p < 0.01), at the end of treatment. After six months, seven out of nine patients reported no pain at all (VAS 0). The WOMAC score improved significantly, from initial values of 35 (range, 10−56) to values of 2 (range, 0−9; p < 0.01). The SF-36 score showed significant improvement after six months in all four domains of physical health (p < 0.01) and in two of the four domains of mental health (p < 0.05). The sports frequency score increased by at least one level in six out of nine patients after six months. Conclusions: The conservative trio-therapy in patients with varus knee OA showed positive initial clinical results: less pain, higher function, better quality of life, and higher sport activity. Further studies are required to evaluate the long-term effect.