OBJECTIVES: To compare the combined effect of Amritadi Guggulu and Mandoora Bhasma with Trayodashanga Guggulu in Osteoarthritis patients. METHODS: A randomized single blind clinical study with pre-test and post-test design was adopted where the patients were given treatment for a period of one month with follow-up. The inclusion criterion of the patients includes Osteoarthritis of knee joints, age group between 30 - 60 years, either gender, and irrespective of occupation and habitat. A total 307 patients of osteoarthritis of knee joint were selected from out-patient and inpatient departments of Muniyal Ayurveda Hospital, Manipal and grouped into A and B 154 and 153. Group A is given Amritadi Guggulu and Mandoora Bhasma and Group B is given Trayodashanga Guggulu.  There were 4 dropouts in group A and 3 in group B. The outcomes were assessed by using paired t-test and p<0.05 was considered as statistically significant. RESULTS: There was significant relief in Joint pain (83.74%), Joint tenderness (80.33%), Joint stiffness (82.83%), Swelling (63.39%), Crepitus (42.26%) and restriction of movement (74.50%) which was statistically significant (p<0.001 ) in group A treated with Amritadi Guggulu and Mandoora Bhasma. In group B treated with Trayodashanga Guggulu was also observed relief in in Joint pain (47.80%), Joint tenderness (78.33%),   Joint stiffness (61.61%),    Swelling (64.28%), and Crepitus (41.86%) restriction of movement (60.46%) which was statistically significant (p< 0.001). In group A there was statistically significant improvement in TLC (15.82%), Hemoglobin (11.58%) and ESR (47.71%) after treatment. In group B also observed statistically significant improvement in TLC (14.52%), Hemoglobin (6.01%) and ESR (43.69%) after treatment. CONCLUSIONS: Ayurveda management with administration of Amritadi Guggulu and Mandoora Bhasma showed good results when compared with patients treated with Trayodashanga Guggulu only. There was an increase in Hb% and decrease in ESR in these patients.