Background: Platelets are irregularly shaped, non-nucleated cytoplasmic bodies derived from fragmentation of megakaryocyte precursors. Objective: This study aimed to evaluate the role of autologous platelet-rich-plasma (PRP) as a monotherapy versus artificial tears (Hyaluronic acid) use for better management of dry eye disease. Patients and Methods: A prospective clinical randomized trial study was conducted on 62 patients with moderate to severe dry eye disease (Schirmer`s test outcomes of 5.5 mm or lower). Patients had been recruited from the Outpatient Clinics of Ophthalmology Department in Zagazig University Hospital during the period from February 2020 to January 2021. They were divided into two equal groups; group A was treated with PRP and group B was treated with artificial tears. Results: There was a significant decrease regarding ocular surface disease index (OSDI) in both groups after treatment, but the improvement was more significantly in PRP group compared to artificial tears group. There was a significant increase in tear break-up time (TBUT) in PRP group only after treatment; although, there was an increase in TBUT in artificial tears group but without statistical significance. There was a significant increase in BCVA in both groups after treatment, but the improvement was more significantly in PRP group compared to artificial tears group. Conclusion: PRP is an interesting alternative therapy in symptomatic dry eye.