Objective To analyze the efficacy and safety of poly-L-lactic acid in patients with nasolabial fold filling. Methods: A total of 80 patients who were treated in our hospital from January 2023 to January 2024 were randomly divided into an observation group and a control group, with 40 cases in each group. The control group was routinely treated with sodium hyaluronate gel filling, while the observation group was treated with poly-L-lactic acid filling. The total effective rate of treatment, the improvement of the severity classification of nasolabial fold wrinkles (WSRS) before and after treatment, and the incidence of adverse reactions (induration, pruritus, pain, nodules, redness and swelling, numbness, bruising) were compared between the two groups of patients. Results: The total effective rate of treatment in the observation group was significantly higher than that in the control group (P<0.05). There was no statistically significant difference in WSRS between the two groups before treatment (P >0.05). After treatment, WSRS improved significantly in both groups, and the improvement of WSRS in the observation group was significantly better than that in the control group (P<0.05). Moreover, the rates of adverse reactions such as induration, pruritus, pain, nodules, redness and swelling, numbness, and bruising in the observation group were significantly lower than those in the control group (P<0.05). Conclusion: Poly-L-lactic acid has a good effect in patients with nasolabial fold filling, which can effectively improve nasolabial fold wrinkles and reduce the occurrence of adverse reactions.