From January 2007 to December 2009, an annual Canadian national surveillance study (CANWARD) tested 2,943 urinary culture pathogens for antimicrobial susceptibilities according to Clinical and Laboratory Standards Institute guidelines. The most frequently isolated urinary pathogens were as follows (number of isolates, percentage of all isolates): Escherichia coli (1,581, 54%), enterococci (410, 14%), Klebsiella pneumoniae (274, 9%), Proteus mirabilis (122, 4%), Pseudomonas aeruginosa (100, 3%), and Staphylococcus aureus (80, 3%). The rates of susceptibility to trimethoprim-sulfamethoxazole (SXT) were 78, 86, 84, and 93%, respectively, for E. coli, K. pneumoniae, P. mirabilis, and S. aureus. The rates of susceptibility to nitrofurantoin were 96, 97, 33, and 100%, respectively, for E. coli, enterococci, K. pneumoniae, and S. aureus. The rates of susceptibility to ciprofloxacin were 81, 40, 86, 81, 66, and 41%, respectively, for E. coli, enterococci, K. pneumoniae, P. mirabilis, P. aeruginosa, and S. aureus. Statistical analysis of resistance rates (resistant plus intermediate isolates) by year for E. coli over the 3-year study period demonstrated that increased resistance rates occurred only for amoxicillin-clavulanate (from 1.8 to 6.6%; P < 0.001) and for SXT (from 18.6 to 24.3%; P = 0.02). For isolates of E. coli, in a multivariate logistic regression model, hospital location was independently associated with resistance to ciprofloxacin (P = 0.026) with higher rates of resistance observed in inpatient areas (medical, surgical, and intensive care unit wards). Increased age was also associated with resistance to ciprofloxacin (P < 0.001) and with resistance to two or more commonly prescribed oral agents (amoxicillin-clavulanate, ciprofloxacin, nitrofurantoin, and SXT) (P = 0.005). We conclude that frequently prescribed empirical agents for urinary tract infections, such as SXT and ciprofloxacin, demonstrate lowered in vitro susceptibilities when tested against recent clinical isolates.