Purpose: To evaluate the clinical efficacy of newly developed guidelines for the diagnosis and management ofdry eye. Methods: This retrospective, multi-center, non-randomized, observational study included a total of 1,612 patientswith dry eye disease who initially visited the clinics from March 2010 to August 2010. Korean guidelinesfor the diagnosis and management of dry eye were newly developed from concise, expert-consensus recommendations. Severity levels at initial and final visits were determined using the guidelines in patients with 90± 7 days of follow-up visits (n = 526). Groups with different clinical outcomes were compared with respect toclinical parameters, treatment modalities, and guideline compliance. Main outcome measures were ocular andvisual symptoms, ocular surface disease index, global assessment by patient and physician, tear film break-uptime, Schirmer-1 test score, ocular surface staining score at initial and final visits, clinical outcome after threemonths of treatment, and guideline compliance. Results: Severity level was reduced in 47.37% of patients treated as recommended by the guidelines. Youngerage (odd ratio [OR], 0.984; p = 0.044), higher severity level at initial visit, compliance to treatment recommendation(OR, 1.832; p = 0.047), and use of topical cyclosporine (OR, 1.838; p = 0.011) were significantly associatedwith improved clinical outcomes. Conclusions: Korean guidelines for the diagnosis and management of dry eye can be used as a valid and effectivetool for the treatment of dry eye disease.