Background: Osteoarthritis (OA) is one of the most common forms of arthritis which is caused by the degeneration of joint cartilage. It is often associated with disability and leads to impairment of quality of life. The clinical picture is similar to the disease Sandhigatavata described in Ayurveda (one among the Vatavyadhi) and is characterized by symptoms such as Sandhi Shoola (joint pain), Sandhishopha (swelling of joint), and Prasarana-Akunchana-Ashakti (difficulty in movements of the joint). The safety of 10 Ayurvedic classical formulations most commonly used in OA was clinically evaluated and the findings are provided in this article. Aim and objective: Critical analysis of clinical safety outcomes of classical Ayurvedic formulations, viz. Vatari Guggulu, Yogaraj Guggulu, Punarnava Guggulu, Maharasnadi Kwatha, Dashmoola Ghrita, Narayan Taila, Kottamchukkadi Taila, Gandharvahasta Taila, Dhanwantara Taila, and Ksheerbala Taila in patients of OA, generated through studies at different Institutes of Central Council for Research in Ayurvedic Sciences (CCRAS). Materials and methods: Data collected from four different clinical studies completed in multiple centers of CCRAS were retrospectively evaluated to assess the safety profile of 10 formulations that are commonly used in OA. Evaluation of safety was done by analyzing liver function tests (LFT) and renal function tests (RFT) before and after the trial period. Paired sample t-test was used to compare mean change from baseline to the 84th day. A p value of <0.05 was considered significant. Conclusion: The findings in four different clinical studies reveal that all ten formulations are clinically safe in patients belonging to various age groups, gender, geographical area, and Prakriti.