Objective: Laparoscopic cholecystectomy (LC), despite its minimally invasive nature, requires effective control of postoperative pain. The use of local anesthetics (LA) has been studied, but the level of evidence is low, and there is little information on important parameters such as health-related quality of life (HRQoL) or return to work. The objective of the study was to evaluate the efficacy of 0.50% levobupivacaine infiltration of incisional sites in reducing POP after LC. Methods: This was a prospective, randomized, double-blind study. Patients undergoing elective LC were randomized into two groups: no infiltration (control group) and port infiltration (intervention group). POP intensity (numerical rating scale, NRS), need for rescue with opioid drugs, PONV incidence, HRQoL, and return to work data, among others, were studied. Results: Two hundred and twelve patients were randomized and analyzed: 105 (control group) and 107 (intervention group). A significant difference was observed in the NRS values (control group mean NRS score: 3.41 ± 1.82 vs. 2.56 ± 1.96) (p < 0.05) and in the incidence of PONV (31.4% vs. 19.6%) (p = 0.049). Conclusions: Levobupivacaine infiltration is safe and effective in reducing POP, although this does not lead to a shorter hospital stay and does not influence HRQoL, return to work, or overall patient satisfaction.