The Study for Monitoring Antimicrobial Resistance Trends (SMART) is a worldwide surveillance program designed to longitudinally monitor the in vitro activity of antimicrobial agents against pathogens that cause intra-abdominal infections (IAIs). In this study, trends in antimicrobial resistance during the period 2006 to 2010 were analyzed at five tertiary-care hospitals in Taiwan. Enterobacteriaceae accounted for the majority (80.9%) of the 2417 Gram-negative isolates, and the two most common species were Escherichia coli (38.8%) and Klebsiella pneumoniae (23.5%). The rates of susceptibility of Enterobacteriaceae isolates to cephalosporins decreased during the study period. Although carbapenems, fluoroquinolones, piperacillin-tazobactam, and amikacin were active in vitro against more than 80% of the Enterobacteriaceae isolates, the activity of carbapenems declined during the study period. Extended-spectrum β-lactamase (ESBL) production in E. coli was steady, but that in K. pneumoniae decreased during the study period. The rate of ESBL-producing species was three-fold higher among patients with nosocomial IAIs than among patients with community-acquired IAIs. The majority of isolates from liver were K. pneumoniae (69%) and very few of those isolates were ESBL producers (0.9%). Pseudomonas aeruginosa (9.3%) and Acinetobacter baumannii (3.8%) were the two most common non-Enterobacteriaceae. P. aeruginosa showed improved susceptibility, whereas A. baumannii showed a rapid development of resistance during the study period. There was marked geographic variation in resistance patterns of the isolates obtained during the study period. Northern Taiwan had the highest rate of ESBL producers and the highest rate of ceftazidime resistance among P. aeruginosa isolates. Central Taiwan had the lowest rate of ESBL producers but the highest rates of carbapenem resistance among P. aeruginosa and A. baumannii isolates. Continuous monitoring and regular updates of epidemiological data are needed to guide appropriate empiric antimicrobial therapy.