Background: Osteoarthritis is a degenerative disorder commonly affecting any joints mostly joints of hands, knees, spine and hips. The disorder occurs when wear and tear of the protective layer of cartilage cushioning the ends of the bones occurs. The symptoms start with pain and stiffness the joints slowly leading to stiffness, tenderness, loss of flexibility, grating sensation, swelling and formation of bone spurs. Osteoarthritis causes deterioration of connective tissue and inflammation of the joint lining. Glucosamine sulphate found in the human body is a naturally occurring chemical which is especially present in the fluid around the joints and is involved in building ligaments cartilage and thick fluid that surrounds the joints. Sulphate part is important for building the cartilage. Sulfasalazine is anti-inflammatory drug and is used to treat and reduce inflammation. In this study the combination of glucosamine sulphate and sulfasalazine is used in combination to test the efficacy in reduction of inflammation and pain in comparison with sulfasalazine alone. Materials and Methods: In this prospective randomized controlled study 60 patients of osteoarthritites between the age group of 18 to 60 years were selected. Patients were divided into two groups (A and B). Age, severity of the disease was taken into consideration while grouping the patients. Group A was treated with Sulfasalazine alone 500mg once a day and group B with combination of Glucosamine Sulphate (oral) 750mg twice a day and Sulfasalazine (oral) 500mg once a day. Assessments of number of swollen joints and VAS and faces pain rating (scale) were carried out once in a month. Results: After six months 67% reduction in number of swollen joints and 76% of duration of morning stiffness in combination therapy was observed compared to 54% and 65% of reduction respectively in sulfasalazine alone. VAS score after six months was found to be 1 in combination therapy and 3 in suflasalazine alone. Conclusion: The study concluded that the combination treatment regimen glucosamine sulfate and oral sulfasalazine improved patient mobility, decreased number of swollen joints and decreased arthritic pain gradually.