The midazolam vs morphine (MIMO) trial showed that patients treated with midazolam had fewer serious adverse events than those treated with morphine. In many patients with acute pulmonary edema, the left ventricular ejection fraction (LVEF) is preserved, at 50% or higher. We aimed to determine whether left ventricular (LV) systolic dysfunction (D), defined by an LVEF of less than 50%, modifies the protective effect of midazolam vs morphine. The MIMO trial randomized 111 patients with acute pulmonary edema to receive intravenous midazolam in 1-mg doses to a maximum of 3 mg (n = 55) or morphine in 2- to 4-mg doses to a maximum of 8 mg (n= 56). We calculated the relative risk (RR) for a serious adverse event in patients with and without systolic LVD. LVEF was preserved in 84 (75.7%) of the patients with acute pulmonary edema. In patients with systolic LVD, 4 patients (26.9%) in the midazolam arm vs 6 (50%) in the morphine arm developed serious adverse events (RR, 0.53; 95% CI, 0.2-1.4). In patients without systolic LVD, 6 patients (15%) in the midazolam arm vs 18 (40.9%) in the morphine arm experienced such events (RR, 0.37; 95% CI, 0.16-0.83). The presence of systolic LVD did not modify the protective effect of midazolam on serious adverse effects (P=.57). The effect of midazolam vs morphine in protecting against the development of serious adverse events or death is similar in patients with and without systolic LVD.