BACKGROUND: Traditional Chinese Medicine categorizes melasma into various syndromes, one of which is the kidney-deficiency and blood-stasis syndrome. Different Chinese medicines are used for each syndrome to achieve a personalized treatment approach, resulting in a more effective outcome. The study aimed to investigate the efficacy and safety of Lutai Danshen Baishao Granules (LDBG) in alleviating melasma and to compare the effects of LDBG in patients with and without kidney-deficiency and blood-stasis syndrome through a real-world, large-sample investigation. METHODS: A multicenter, prospective, nonrandomized, observational trial was conducted from December 2021 to May 2023, recruiting 1000 female participants with melasma. After enrollment, participants were divided into Group A (kidney-deficiency and blood-stasis syndrome) and group B (non-kidney-deficiency and blood-stasis syndrome) based on the traditional Chinese medicine (TCM) syndrome scale. General physical signs, melasma indicators, Dermatology Life Quality Index, and TCM syndrome scores were recorded before and after the intervention. The long-term effectiveness was assessed 2 months after the intervention ended. RESULTS: Following the intervention, melasma-related indicators and TCM syndrome scores were significantly lower than those before the intervention (P <
.001). Compared to Group B, Group A showed a more significant reduction in the total area of melasma and the Melasma Area and Severity Index score (P <
.05). The reduction in melasma area was also more pronounced in Group A (group A: 425.00 vs group B: 312.50, P <
.001). Two months after the intervention, intergroup and intragroup comparisons revealed that LDBG had a long-term effect with a lower tendency for recurrence, and the long-term effect in Group A was better than in group B (P <
.05). The overall incidence of adverse events during the trial was 1.2%. CONCLUSION: LDBG can reduce facial melasma and improve TCM syndromes, particularly in cases of melasma associated with kidney-deficiency and blood-stasis syndrome, with high safety and low risk of relapse.