Objective: The objective of this study was to evaluate the safety and effectiveness of photoselective vaporization of the prostate (PVP) in the treatment of patients with benign prostatic hyperplasia (BPH) on anticoagulant or antiplatelet therapy. Background: The gold standard of surgical treatment of BPH is transurethral resection of the prostate (TURP). Since the risk of complications associated with TURP is still significant, there is a continuous search for safer and equally effective procedures. One of them is PVP with a 532nm potassium-titanyl-phosphate/lithium triborate (KTP/LBO) laser. Materials and methods: A total of 109 patients underwent PVP with the use of the GreenLight HPS 120 W laser. Sixty-five (59.6%) of the patients were on anticoagulants or antiplatelet drugs, whereas 44 (40.4%) patients were not. Various objective and subjective parameters were evaluated intra- and postoperatively along with a 5-year follow-up to compare the results and safety of PVP in these two groups of patients. Results: No difference between the groups was found in intraoperative parameters, including operation and lasing time, as well as laser energy used. Also, no intraoperative complications were observed. There was no significant bleeding in any of the groups, and none of the patients required a blood transfusion. Catheterization and hospitalization time did not differ between both groups, and during the 5-year follow-up period, good objective and subjective results were observed, and the complication rates were comparable between the groups. Conclusions: Our results demonstrate that PVP for patients with BPH is an effective and safe procedure with satisfactory long-term outcomes. Anticoagulant and antiplatelet drugs did not significantly influence the results, or the complication rates.