BACKGROUND: Acinetobacter baumannii (AB) has evolved a variety of resistance mechanisms and exhibits unpredictable susceptibility patterns, making it difficult to select empiric therapy. OBJECTIVE: To examine US secular trends in the resistance of AB in respiratory infections and blood stream infections (BSI) to antimicrobial agents whose effectiveness is supported in the literature DESIGN: Survey. METHODS: We analyzed 3 time periods (2003-2005, 2006-2008, 2009-2012) in Eurofins' The Surveillance Network for resistance of AB to the following antimicrobials: carbapenems (imipenem, meropenem, doripenem), aminoglycosides (tobramycin, amikacin), tetracyclines (minocycline, doxycycline), polymyxins (colistin, polymyxin B), ampicillin-sulbactam, and trimethoprim-sulfamethoxazole. Resistance to ≥3 drug classes defined multidrug resistance (MDR). RESULTS: We identified 39,320 AB specimens (81.1% respiratory, 18.9% BSI). The highest prevalence of resistance was to doripenem (90.3%) followed by trimethoprim-sulfamethoxazole (55.3%), and the lowest to colistin (5.3%). Resistance to carbapenems (21.0% in 2003-2005 and 47.9% in 2009-2012) and colistin (2.8% in 2006-2008 to 6.9% in 2009-2012) more than doubled. Prevalence of MDR AB rose from 21.4% in 2003 to 2005 to 33.7% in 2006 to 2008, and remained stable at 35.2% in 2009 to 2012. In contrast, resistance to minocycline diminished from 56.5% (2003-2005) to 30.5% (2009-2012). MDR organisms were most frequent in nursing homes (46.5%), followed by general ward (29.2%), intensive care unit (28.7%), and outpatient setting (26.2%). CONCLUSIONS: Resistance rates among AB to such last-resort antimicrobials as carbapenems and colistin are on the rise, whereas that to minocycline has declined. Nursing homes are a reservoir of resistant AB. These trends should inform not only empiric treatment of serious infections, but also approaches to infection control.