There are no standard choices on antifungal drugs for talaromycosis due to various factors, and related studies are also limited. This study summarizes and analyzes efficacy of different antifungal drugs for patients with talaromycosis, which can provide more reference evidence for drugs’ choices in practice. We conducted a meta-analysis on prognostic impacts of different antifungal drugs against talaromycosis, and primary outcome was all-cause mortality. A total of 975 patients from 8 studies were included. One of the 8 studies was a randomized controlled trial and the others were retrospective studies. Among these patients, 582 cases were initiated with amphotericin B, 31 cases died (9.28%). The other 393 cases were initiated with itraconazole, and 54 cases died (14.00%). The initial use of amphotericin B for talaromycosis significantly reduced mortality compared with itraconazole (risk ratio (RR): 0.61; 95% confidence interval (CI): 0.41–0.90; P=0.01; I²=4%). Initial treatment with amphotericin B for talaromycosis in different regions (internal and external) and studies (sample size<100) had no obvious prognostic advantages over itraconazole (RR: 0.60, 95% CI: 0.32–1.13; P=0.11; I²=44%; RR: 0.61, 95% CI: 0.37– 1.00; P=0.05; I²=0%; RR: 0.71, 95% CI: 0.39–1.29; P=0.26; I²=0%, respectively). However, when study's sample size was ≥ 100, the mortality of amphotericin B group was significantly reduced (RR: 0.54, 95% CI: 0.32– 0.92; P=0.02; I²=46%). In conclusion, amphotericin B is a better choice as initial therapeutic drug for talaromycosis.