Background: Regenerative medicine may be defined as the process of replacing or regenerating human tissues or cells of humans to restore or to get very near to normal function of human life. Biological tissues found in humans such as blood, fat, bone marrow are the main resources of regenerative medicine which help in natural process of healing of soft tissue. Extracorporeal shock wave therapy (ESWT) is a physical modality that helps in enhancing healing process of soft tissues. Osteoarthritis of the knee joint is a gradually progressive degenerative condition with the loss of articular cartilage. The early stages of disease are managed conservatively with the aim of retarding the rate of cartilage destruction. Methods: A total of 80 patients underwent the novel triple therapy. The objective is to find out the potential of combination therapy in early degenerative disease of knee with the aim of reduction of inflammation. A protocol was developed which involved three injections of platelet rich plasma (PRP), six sessions of combined ESWT and physiotherapy. Results: Evaluation was mainly based on WOMAC/KSS/VAS scores. Patients in stage 1 and 2 (55+15=70) had excellent results for 36 months, patients in stage 3 (10 cases) had satisfactory outcome at 24 months. Conclusions: Triple therapy is an alternative treatment or in few cases a definitive treatment in degenerative disease of knee joint where medical and surgical management has minimal or no role. Triple therapy in mild to moderate osteoarthritis of knee joint has better outcome.