Objective: To compare the efficacy of lacrimal probing and syringing among 3% solution of sodium chloride and/or 0.2 mg/ml mitomycin-C as an adjunctive medication in reducing epiphora symptom. Study design: A prospective, randomized, 2 by 2 factorial design study. Setting: Department of Ophthalmology, Phramongkutklao Hospital. Research medthodology: 48 of nasolacrimal duct obstruction patients with epiphora symptom were randomly assigned to receive either normal saline solution (NSS) or 3% solution of sodium chloride (NaCl) or 0.2 mg/ml mitomycin-C (MMC) solution or combined 3% NaCl with 0.2 mg/ml MMC solution, during office probing and syringing repeatedly at week 0, weeks 2 and 4. An assessment of epiphora with visual analogue scale (VAS), fluorescein dye disappearance test (FDDT) and Jones test were evaluated at week 0, weeks 2, 4, 8 and 12. Results: Probing and syringing was successfully reducing epiphora symptom and improvement of FDDT and Jones test. MMC group showed a significant reduction in mean difference of VAS score compared with NSS group (p<0.01), 3% NaCl (p<0.01) and combined 3% NaCl with MMC solution (p<0.05). No complication or adverse event was found. Conclusion: 0.2 mg/ml mitomycin-C solution of was the most effective medication for office probing and syringing in reducing epiphora symptom in nasolacrimal duct obstruction patients.