Objective To explore whether voriconazole combined with caspofungin can improve the prognosis of critically ill patients with invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU). Methods Clinical data of patients clinically diagnosed and confirmed with IPA in ICU from June 2014 to June 2019 were retrospectively collected, difference in clinical efficacy, acute kidney damage and 42-day survival status after antifungal therapy between voriconazole monotherapy group (monotherapy group) and voriconazole combined with caspofung group (combination group) were compared, risk factors for death in critically ill patients with IPA were analyzed. Results A total of 35 critically ill patients with IPA were included, 25 cases (71.4%) in monotherapy group and 10 cases (28.6%) in combination group. There were no significant differences in overall clinical effective rate, impact on renal function and 42-day survival status between combination group and monotherapy group (all P>0.05). Multivariate Cox regression analysis showed that combination therapy (HR=0.664, 95%CI: 0.222-1.984, P=0.464) was not an independent influencing factor for death in critically ill patients with IPA. Conclusion Voriconazole combined with caspofungin can't improve the prognosis of critically ill ICU patients with IPA.