Background: treatment of dry eye disease (DED) depends on minimizing inflammation and improving various components of the tear film. Artificial tears remain an important part of patient comfort, with many lipid- and gelbased formulations for a healthy ocular surface. Objective: the work aimed to evaluate the role of autologous platelet-rich plasma (PRP) as a monotherapy for treatment of dry eye disease, versus artificial tears use. Patients and Methods: a prospective comparative study. The study included 55 eyes of 30 patients with moderate to severe dry eye disease. The study was performed at Ophthalmology Department in Alazhar University Hospitals. Results: in our study PRP group of patients all are improved in all parameters and all of them were statistically significant. Symptoms OSDI score decreased indicating improvement in 86.6% of patients. TBUT improved in 66.6% of cases. CFS improved up to disappearance of staining in 33% of cases and fair improvement in 53.3%, total improvement was 86.6%. Schirmer test improved in 40% of cases. BCVA improved in 26.6% of patients, improvement was not more than one line. Conclusion: PRP is very effective in treatment of moderate and severe cases of DED at the level of subjective symptoms, TBUT, CFS, BCVA, and Schirmer test.