Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) often receive antibacterial prophylaxis. Antibacterial agents can cause elevations in the prothrombin time and international normalized ratio (INR). The impact of prophylactic antibacterials on the coagulation profiles and bleeding risk in patients with AML/MDS is unknown. We evaluated patients with AML or MDS who were being admitted to the hospital. The cohort was divided into two groups of patients: (1) those receiving and (2) those not receiving prophylactic antibacterials, at the time of admission. We conducted a retrospective cohort study of adult patients with AML/MDS admitted to Yale-New Haven Hospital between 2015–2019. The study was approved by the Yale Institutional Review Board. Inclusion criteria included patients >18 years old with a diagnosis of AML or MDS admitted to the hospital. We identified 150 individual patient encounters with active AML/MDS admitted to Yale-New Haven of which 32 occurred while on and 118 while off antibacterial prophylaxis. Median duration of pre-admission antibacterial exposure was 2 (range: 0.07–24) months. Patients on antibacterial prophylaxis had higher INR (median 1.14 vs. 1.03, p = 0.0002), and higher partial thromboplastin time prolongation (median 26.5 vs. 24.3, p < 0.0014), than patients without antibacterial prophylaxis. Patients without antibacterial prophylaxis had higher rates of bleeding using the ISTH-defined criteria (24.6% vs. 6.3%, p = 0.043), including higher rates of ISTH major (2 vs. 0) and clinically relevant bleeding (9 vs. 0). Patients with AML/MDS on antibacterial prophylaxis were more likely to have an abnormal coagulation profile when compared with their counterparts not on prophylaxis. Conversely, rates of bleeding were higher in patients not on prophylaxis. These data suggest that prophylactic antibacterials do not increase bleeding risk in patients with AML/MDS.