Acquired Obliteration of the Proximal Lacrimal Drainage System Purpose: We present a series of patients with acquired obliteration of one or more components of the proximal lacrimal drainage system, including puncta and canaliculi. This finding was noted with and without other obstructions or stenoses of the lacrimal drainage system. Review of these patients in search of possible risk factors for this condition and histopathology of two patients are presented. Methods: Medical records of patients treated at the Massachusetts Eye and Ear Infirmary between 2010 and 2016 with diagnosis codes of lacrimal punctum stenosis, stenosis of unspecified lacrimal punctum, epiphora due to insufficient drainage, and epiphora not otherwise specified were retrospectively reviewed. Patients were excluded if there was a history of congenital punctal agenesis, trauma, or any other identifiable etiology of lacrimal system obstruction. Results: Twelve patients were identified with obliterated puncta. Most patients were female (n = 11, 91.7%) and Caucasian (n = 9, 75%). The mean age was 61 years (median 62, range 22–90 years). Clinical findings ranged from one involved punctum to all four puncta, and associated ipsilateral canalicular obstruction was noted in 4 patients (33.3%). The inferior puncta were the more frequently affected structures (61.5%) compared to the superior puncta (38.5%). Nine patients (75%) reported use of topical ophthalmic medications prior to onset of symptoms. The most frequent class of medication implicated was topical antibiotics; however, patients often used a combination of medications. In 2 cases, pathological specimens of the canaliculi revealed absence of a canalicular lumen. Conclusions: Although various combinations of lacrimal system stenoses and obstructions have been described, acquired punctal obliteration is an under-recognized entity. These cases differ from typical punctal stenosis in that the puncta are completely obliterated, and no indication of a punctal opening is clinically detectable. In this study, 3 patients had previously documented normal lacrimal irrigation. The ipsilateral canaliculi were also found to be obstructed in a third of patients. Two patients had complete absence of a canalicular lumen on histopathology. The predominance of inferior punctum involvement, patient history of symptom onset after ipsilateral medication use, and known prior patent irrigation in several cases support the hypothesis that these cases represent a severe yet insidious idiosyncratic reaction to topical medication.