Venous lakes (VLs) are benign malformations often localized in the lips, therefore impacting the self-confidence of patients. In the present study, the use of a Nd:YAG laser according to a defined protocol with a low level of absolute energy (4.9 J) is proposed for the treatment of VLs of the lips. A total of 47 patients with 50 labial VL were treated with a Nd:YAG in one laser session without local anesthesia. The area reduction was evaluated according to the Vlachakis criteria 7 and 30 days after the laser application. Additionally, oral discomfort was rated according to the Numeric Rating Scale (NRS) during and 24 hours after the procedure. All patients achieved complete clinical healing within 30 days after the laser application. In particular, patients with VL with a diameter ≤ 6 mm (62.1%) achieved a complete resolution after 7 days (p-value < 0.001). Such patients reported little or no discomfort (NRS 0 to 3) during the laser session and no discomfort after 24 hours (p-value < 0.001). No major complications were reported, and no recurrence was observed at 2-year follow-up. These findings suggest that Nd:YAG laser treatment could be an effective and well-tolerated approach to the aesthetic treatment of labial VL.