Abstract: OBJECTIVE To establish and implement a pharmacist-led proactive intervention model for voriconazole (VCZ) therapeutic drug monitoring (TDM) and observe the effects on clinical treatment process and treatment outcomes. METHODS The clinical data were collected from 513 patients who were treated in Wuhan No. 1 Hospital in 2019 (the passive intervention period) and 2023 (proactive intervention period) and were retrospectively analyzed. 176 patients were finally included from each of the two groups by propensity score matching in a 1∶1 ratio. The proactive intervention mode was established based on five major core strategies， including standardized decision-making， pre-emptive risk interception， intelligent reporting， multidimensional education for healthcare professionals and patients， and multidisciplinary collaboration. The effectiveness was observed and compared between the two intervention modes through evaluation of coverage rate of TDM， therapeutic rate， incidence of voriconazole-associated liver damage， therapeutic discontinuation rate due to adverse effects， adoption rate of clinical pharmacists' recommendations， and overall effective rate of treatment. RESULTS The coverage rate of voriconazole TDM was higher during the proactive intervention period (84.01%%) than during the passive intervention period (53.37%) (P＜0.001); the TDM therapeutic rate was higher during the proactive intervention period (70.10%%) than during the passive intervention period (55.81%) (P＜0.001)， the supratherapeutic rate and subtherapeutic rate were lower during the proactive intervention period (15.21%，14.69%) (P=0.004) than during the passive intervention period (23.51%， 20.68%) (P=0.032); the adoption rate of clinical pharmacists' recommendations and the overall effective rate of treatment were higher during the proactive intervention period (88.92%， 86.36%) (P＜0.001) than during the passive intervention group (65.16%， 67.61%) (P＜0.001); the incidence of voriconazole-associated liver damage and the therapeutic discontinuation rate due to adverse effects were lower during the proactive intervention period (7.39%，5.11%) (P＜0.001) than during the passive intervention period (19.32%， 18.18%) (P＜0.001). CONCLUSIONS This proactive intervention mode can effectively raise the coverage rate and precision of voriconazole TDM， remarkably improve the treatment outcomes of the patients， and reduce the risk therapeutic toxicity， which reflects a pivotal shift in the pharmacist's role from passive data provision to active participation in therapeutic decision-making， providing a replicable pathway for the individualized treatment of high-risk drugs and the practice of value-based healthcare.