Background: Anti-glaucoma eye drops have been investigated due to their production of fibrotic changes on the conjunctival surface, undermining the functioning of the upper lacrimal drainage system. We aimed to assess whether these effects may impair the effectiveness of endoscopic endonasal dacryocystorhinostomy (EE-DCR). Methods: This is a single-center observational retrospective study on EE-DCR via a posterior approach. Resolution of epiphora and dacryocystitis were analyzed after 1 (T1) and 6-months (T2) from surgery. Surgical success was defined as anatomical (patency at irrigation, no recurring dacryocystitis) or complete (zeroing of Munk score). Results: Twenty patients (32 sides) were enrolled. Preoperatively, 93.75% (n = 30/32) presented severe (Munk 3–4) epiphora and 68.75% (n = 22/32) recurrent dacryocystitis. At T1, 50.0% (n = 16/32) were referred with residual epiphora (Munk ≥ 1) and 18.75% (n = 6/32) dacryocystitis. At T2, 31.25% (n = 10/32) still complained of epiphora (Munk ≥ 1) and 6.25% (n = 2/32) dacryocystitis. Difference of outcomes at aggregate and paired timepoints (except for T1 versus T2) resulted in statistical significance (p < 0.05). At T2, 22 (68.75%) complete, 8 (25.0%) anatomical successes and 2 (6.25%) surgical failures were observed. Conclusions: Despite the chronic uptake of anti-glaucoma eye drops, EE-DCR guaranteed high rates of clinical relief from epiphora and remarkable decreases in the rates of recurrent dacryocystitis.