Objectives: This study intends to evaluate early hemorrhagic complications after holmium laser enucleation of the prostate (HoLEP) in patients undergoing antithrombotic therapy. Methods: The data of patients undergoing HoLEP between January 2020 and February 2023 were retrospectively analysed. Patients were clustered into three groups: (1) no antithrombotic therapy; (2) antiplatelet (AP) therapy; and (3) anticoagulant (AC) therapy. Pre-, intra-, and post-operative variables were compared. A logistic regression model was built to identify predictors of post-operative hemorrhagic complications. Results: A total of 338 patients underwent HoLEP, including 212 who received no antithrombotic therapy (62.7%), 76 who received AP (22.5%), and 50 who received AC (14.8%). Intra-operative outcomes did not show any significant difference. A significant difference was observed in terms of catheterisation time (p = 0.001) and length of hospital stay (p < 0.001), favouring patients who did not receive antithrombotic therapy. Early post-operative hemorrhagic complications (<30 days) included re-admissions for macrohematuria (3.5%), transfusions (2.4%), and endoscopic re-interventions for bleeding (1.2%). A comparison between the groups showed significant differences for both re-admission (p < 0.001) and transfusion rates (p = 0.01), favouring patients who did not receive antithrombotic therapy. The re-intervention rate did not show any significant difference between the groups (p = 0.1). In multivariate analysis, AC therapy was identified as an independent predictor of those complications (OR 4.9, p = 0.005). Conclusions: HoLEP is a safe and effective procedure for patients undergoing antithrombotic therapy. Both AP and AC therapies are associated with longer catheterisation and hospitalisation times. AC therapy is shown to be a predictor of minor post-operative hemorrhagic complications.