Background and Objective: Epiphora is a common ophthalmological complaint worldwide with a broad differential diagnosis. One of the etiologies of epiphora is punctual stenosis, specially acquired causes, which has a variety of therapeutic surgical options. The purpose of this study was to compare the clinical outcomes and tolerances of multi-action eye drops and single-action eye drops for the medical treatment of epiphora in eyes with acquired punctum stenosis. Methodology: This multi-center randomized clinical trial carried out between September to November 2024 at the Suez General Hospital and Port Said University Hospital Ophthalmic outpatient clinics on 100 individuals complaining from epiphora due to acquired punctum stenosis. Patients were assessed based on Munk epiphora, Fluorescein dye disappearance test (FDDT) and kashkouli punctal stenosis scores, 50 patients were managed with multi-action eye drop (containing antibiotic, steroid and decongestant) and another 50 patients were managed by single action eye drop (containing decongestant only), follow ups were every two weeks till two months by clinical examination, IOP measurement, assessing epiphora relief by Munk epiphora grading improvement, assessing functional relief by Fluorescein dye disappearance test (FDDT) improvement and bitter taste of multi-action eye drop in patient throat ,and finally assessing morphological relief by kashkouli punctum stenosis grading improvement. Results: A total of 100 patients were included in the study with a mean age of 55.4 ± 10.2 years. There was a statistically significant difference in the Munk grading and FDDT along the follow-up period compared to the baseline values (P< 0.001). Multi-action eye drops showed 80.0% success after first 2 weeks of treatment and reached to 92.0% after 4 weeks of treatment, while single action eye drops showed only 10.0% success after 2 weeks until the last follow-up after 8 weeks. Subjective assessment of the improvement in both groups using Munk's test, FDDT and the bitter taste. Conclusion: Multi-action eye drops as a medical treatment can control the epiphora in eyes with acquired punctal stenosis and accompanied by both functional and morphological success in the form of improvement of the Munk's test, FDDT score, kashkouli punctal stenosis grading.