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Antimicrobial stewardship programs have been shown to help reduce the use of unnecessary antimicrobial agents in the hospital setting. To date, there has been very little data focusing on high-use areas, such as the medical ICU. A prospective intervention was done to assess guideline compliance, antimicrobial expenditure, and healthcare cost when an infectious disease fellow interacts regularly with the medical ICU team.A 3-month retrospective chart review was followed by a 3-month prospective intervention the following year. Two hundred forty-six total charts were reviewed to assess generally accepted guideline compliance, demographics, and microbiologic results.Twenty-four-bed medical ICU at an 861-bed tertiary care, university teaching hospital in North Carolina.Patients receiving antibiotics in the medical ICU.During the intervention period, the infectious disease fellow reviewed the charts, including physician notes and microbiology data, and discussed antimicrobial use with the medical ICU team.Antimicrobial use, treatment duration, Acute Physiology and Chronic Health Evaluation II scores, length of stay, mechanical ventilation days, and mortality rates were compared during the two periods.No baseline statistically significant differences in the two groups were noted (i.e., age, gender, race, or Acute Physiology and Chronic Healthcare Evaluation II scores). Indications for antibiotics included healthcare-associated (53%) and community-acquired pneumonias (17%). Significant reductions were seen in extended-spectrum penicillins (p = 0.0080), carbapenems (p = 0.0013), vancomycin (p = 0.0040), and metronidazole (p = 0.0004) following the intervention. Antimicrobial modification led to an increase in narrow-spectrum penicillins (p = 0.0322). The intervention group had a significantly lower rate of treatments that did not correspond to guidelines (p < 0.0001). There was a reduction in mechanical ventilation days (p = 0.0053), length of stay (p = 0.0188), and hospital mortality (p = 0.0367). The annual calculated healthcare savings was $89,944 in early antibiotic cessation alone.Active communication with an infectious disease practitioner can significantly reduce medical ICU antibiotic overuse by earlier modification or cessation of antibiotics without increasing mortality. This in turn can reduce healthcare costs, foster prodigious education, and strengthen relations between the subspecialties.