Suppression of resistance in a dense population of Pseudomonas aeruginosa has been shown with optimized quinolone exposures. However, relevance to the beta-lactams is questionable because of the unknown impact of the inoculum effect. We explored the bactericidal activity of various beta-lactams and their propensity to suppress spontaneous resistance. Minimal killing and resistance selection was seen with piperacillin, most likely due to the inoculum effect. Moderate and significant killing was seen at 24 h with ceftazidime and meropenem, respectively; however, regrowth and selective resistance amplification was apparent at 48 h. Our results suggest that different beta-lactam subclasses have a distinct killing profile and propensity to suppress resistance against a dense population of P. aeruginosa. The pharmacodynamics of each subclass of agent should be examined individually, and investigations longer than 24 h may be necessary to fully evaluate the relationship between drug exposures and the likelihood of resistance suppression.