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Background and Importance Autologous serum eye drops (ASED) are a therapeutic option for severe ocular surface diseases, especially in patients unresponsive to conventional treatments. Their composition, similar to natural tears, promotes healing and symptom’s relief. However, evidence on safety and patient satisfaction in real-world practice is scarce.Aim and Objectives To evaluate the impact of ASED on visual acuity (VA), ocular symptoms, safety, and patient-reported satisfaction in refractory ocular diseases in real-world practice.Material and Methods Retrospective and observational study including patients ≥18 years treated with ASED (August 2023–August 2024) for severe dry eye, Sjögren’s syndrome, corneal injury, or other refractory ocular diseases. Data collected: demographics, diagnosis, VA, ocular symptoms and adverse events (AE). Effectiveness was assessed through change in VA and patient-reported symptom improvement at baseline and after 6 months. Safety was evaluated via reported AE. Satisfaction was measured by the validated questionnaire Treatment Satisfaction Questionnaire for Medication (TSQM v1.4, Spanish version), via telephone, scoring four domains (effectiveness, side effects, convenience, global satisfaction; scale 0–100; positive ≥75). Statistical analysis included descriptive measures and pre–post comparisons.Results Thirty-nine patients were included (89.7% female; mean age 66 ± 11.5 years). Diagnoses: dry eye (n=22), Sjögren’s syndrome (n=7), corneal injury (n=7), others (n=2). Thirty-five patients had completed VA data. Overall, 40% showed general VA improvement and 40% remained stable. Symptom relief was reported by 71.8% of patients, including improvement in dryness (n=10), foreign body sensation (n=6), itching (n=4), pain (n=4), irritation (n=3) and corneal ulcers (n=1). No AE were reported. TSQM scores (n=34) were: effectiveness 76.8 ± 24.3 (67.6% ≥75), side effects 100 ± 0.0 (100% ≥75), convenience 77.8 ± 16.4 (58.8% ≥75), global satisfaction 84.9 ± 23.8 (85.3% ≥75).Conclusion and Relevance In real-world practice, ASED achieved high patient-reported satisfaction and significant symptom relief in refractory ocular diseases, with an excellent safety profile, even without measurable VA changes. These findings support ASED as a valuable therapeutic option for patients with limited alternatives and highlight the importance of incorporating patient-reported outcomes in routine ophthalmic care.Conflict of Interest No conflict of interest