Romiplostim is a Food and Drug Administration (FDA)-approved therapy for immune thrombocytopenia (ITP). Biosimilar is a biological product that has no clinical meaningful difference from an existing FDA-approved reference product. It has a potential of lowering health-care-related cost. Biosimilar of romiplostim can be made available to patients with ITP at a low cost and can be beneficial in providing the best therapy. Thus, the efficacy and safety of biosimilar romiplostim (ENZ110) was compared with innovator romiplostim (Nplate) with respect to platelet response in patients with chronic ITP. This was a prospective, multicenter, randomized, and double-blind clinical trial. Patients with chronic ITP, aged 18–65 years, were enrolled in a study and were randomized to receive either ENZ110 or Nplate in a 3:1 ratio for a treatment period of 12 weeks, respectively. After completion of the treatment period, the patients were followed-up for one week to evaluate the platelet response and to monitor the adverse events (AEs). Over the duration of 12 weeks, platelet response of > 50 × 109/L was achieved in 85.3% patients treated with ENZ110 and in 75.0% patients treated with Nplate in per protocol population. In intent-to-treat population, 83.8% patients with ENZ110 and 76.9% patients with Nplate achieved a platelet response of > 50 × 109/L. In the ENZ110 group, 111 AEs were recorded in 66.7% patients, while 18 AEs were reported in 61.5% patients in the Nplate group. The study demonstrated non-inferiority with comparable efficacy and safety between biosimilar romiplostim and innovator romiplostim in patients with chronic ITP.Trial registration number and date of registration: CTRI/2019/04/018614.