Background: Primary osteoarthritis knee is a degenerative joint disease which is becoming a burden on the society as the aging population is increasing day by day due to increased healthcare facilities. Often, patients need nonsteroidal antiinflammatory drugs (NSAIDs) for pain reduction along with disease-modifying osteoarthritic drugs, and NSAID use in aged population is itself a risk factor for developing gastrointestinal, renal, and cardiovascular side effects. Many patients need intra-articular injection of steroid or high molecular weight (HMW) hyaluronate to reduce pain specially in those who do not respond to NSAID and are in high-risk group for developing side effects of NSAIDs. This study is an attempt to compare the effectiveness of intra-articular injection of steroid (i.e., depot-methylprednisolone) and steroid plus HMW hyaluronate in primary osteoarthritis knee, as literature survey revealed that there is a scarcity of study which compared the effectiveness of intra-articular injection of steroid and steroid plus HMW hyaluronate in primary osteoarthritis knee. Materials and methods: This is a single-blind randomized parallel group study conducted in the Department of Physical Medicine and Rehabilitation, Institute of Postgraduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, for a period of 18 months taking 30 subjects in each group. Patients with Kellgren–Lawrence radiological grading II and III of primary osteoarthritis knee were taken in the study group. Patients who did not cooperate to receive intervention, patients with secondary osteoarthritis knee, who had history of allergy to any component of viscosupplementation, patients with grade I and IV osteoarthritis knee, with gross knee instability, patients who received intra-articular injection in the last one year, and patients having contraindications of intra-articular injection were excluded from the study. Visual analogue scale pain and fifty feet walk time were the primary outcome measures. After taking clearance from the institutional ethical committee, patients were selected based on the inclusion and exclusion criteria, and the baseline assessment was done on the parameters. The selected patients were divided into two groups randomly. Written informed consent was taken from all patients before interventions. One group received intra-articular injection of steroid (depot methylprednisolone 40 mg) and another group received intra-articular injection of steroid plus HMW hyaluronate in a single sitting. Injections were administered under strict aseptic condition. After administering injections, the patients assessed at an interval of 6 weeks (visit-2) and 12 weeks (visit-3) using the parameters mentioned above. The results have been analyzed according to the standard statistical methods to fulfill the aims and objectives of the study. Discussion: A majority of patients were females with a mean age of 56.26 years with standard deviation 10.364. Most of the patients had K–L grade III osteoarthritis knee with mean body mass index (BMI) 22.60 and with standard deviation 1.708. Visual analogue scale pain and fifty feet walk time improved in both groups in all visits, but the difference of improvement between groups was not statistically significant.