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Introduction Clozapine-induced sialorrhea (CIS) is a common, treatment-limiting and stigmatizing side effect. All systemic agents that are used for hypersalivation may increase clozapine side effects such as blood pressure changes, constipation, or arrythmias. Oral application of topical anti-muscarinic agents may be a low side effect option for treatment of CIS. Objective The aim of this case report was to propose an off-label treatment of tropicamide drops to CIS and to stimulate further investigation. Case report A 33-year-old male inpatient with schizophrenia has been on clozapine 800 mg and amisulpride 600 mg/day. His drooling was occasional and severe as drool drips off his chin during the day and night. Wet area over the pillow, visual analog scale (VAS), the short form of health survey (SF-36), UKU side effect rating scale, scale for the assessment of negative symptoms (SANS), scale for the assessment of positive symptoms (SAPS) were applied at baseline and in one-week intervals. Oral application of one drop of tropicamide % 0.5 (5 mg/mL) to left and one drop to right side before going to bed in the first week and two drops to each side were administered subsequently. Informed consent was given by the patient. Results No psychological, neurological, autonomic and other side effects were observed associated with tropicamide. On VAS, the patient rated hypersalivation 5/7 at baseline, 4/7 after one drop each, 3/7 after two drops each. Conclusions The reduction of CIS by oral use of tropicamide eye drops is promising and should be explored with randomized controlled trials. [ABSTRACT FROM AUTHOR]