ABSTRACTManagement of pulmonary mucormycosis includes intravenous liposomal amphotericin-B (L-AmB), followed by posaconazole or isavuconazole. We aimed to determine the optimal L-AmB duration before switching to triazole therapy. Using data from a retrospective study in France, we performed an emulated trial evaluating stopping L-AmB after 14 days (short treatment) versus continuing L-AmB (long treatment). The benefit of combination L-AmB therapy was also investigated. A cloning, censoring, and weighting approach was used to account for immortal time and indication biases. Ninety-four cases of pulmonary mucormycosis were included, of which 35% had dissemination. Eighty-nine patients received L-AmB first-line therapy for a median of 25 (IQR: 12–54) days, including 18 patients as combination therapy. L-AmB was discontinued for adverse events in 16/89 patients (18%). Treatment was switched to posaconazole (n = 38) or isavuconazole (n = 9) in 47 cases and was switched back to L-AmB due to disease progression in 11/47 (23%) cases. Overall, the 180-day mortality was 54%. Diagnosis in the ICU, dyspnea at diagnosis, disseminated disease, and ground-glass opacities on chest CT scan were associated with increased mortality. No difference in 180-day survival was found between patients receiving short or long L-AmB treatment (HR=0.80, 95% CI [0.29–1.99]) and between patients receiving L-AmB alone or in combination (HR=1.14, 95% CI [0.56–2.32]) in emulated trials, although confidence intervals were wide. Switching to triazole therapy after 14 days of L-AmB treatment was as effective as longer durations while reducing L-AmB side effects. Combination therapy did not improve prognosis. These results could inform randomized clinical trials assessing different first-line therapeutic strategies for pulmonary mucormycosis.