Background: The objective of the study was to assess health care providers' (HCPs) knowledge and attitude toward antimicrobial resistance (AMR) and implement an antimicrobial stewardship program (ASP) in a long-term acute care hospital (LTACH). Methods: A questionnaire on antibiotic use and resistance was administered to HCP in an LTACH in Detroit, Michigan, between August 2011 and October 2011. Concurrently, a retrospective review of common antibiotic prescription practices and costs was conducted. Then, a tailored ASP was launched at the LTACH followed by 2-phase postimplementation assessment aiming at evaluating the impact of the ASP on antibiotic expenditure. Results: Of all respondents (N = 26), 65% viewed AMR as a national problem, but only 38% perceived AMR as a problem at their facility. Most respondents were familiar with infections caused by resistant organisms such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and extendedspectrum beta-lactamase; however, only 35% expressed confidence in treating infected patients. In the preimplementation phase, 15% of antimicrobial doses were inappropriate and 10 of 13 de-escalation opportunities were missed, resulting in additional (sic) 23,524.00 expenditure. In the first postimplementation phase, there was a 42% and 58% decrease in the use of daptomycin and tigecycline, respectively, resulting in (sic) 55,000 savings. In the second postintervention phase, total antimicrobial cost for treating a cohort of 28 patients in 2016 and 2017 was (sic) 26,837.85 and (sic) 22,397.15, respectively. Conclusions: Introduction of an ASP in an LTACH improves antimicrobial prescribing practices, reduces cost, and is sustainable. (C) 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.