We conducted a controlled clinical comparison of PF Plus, the new pediatric medium with adsorbent polymeric beads, versus the charcoal-containing PF medium in the BacT/Alert blood culture system. A total of 2,381 pediatric cultures were enrolled, and 1,703 (71.5%) were deemed to be compliant and acceptable for analysis. Seventy-two cultures (4.2%) had a positive result with 80 clinically significant microorganisms. The results showed that the PF Plus medium yielded more clinically significant microorganisms than the BacT/Alert system (P < 0.05). In addition, the PF Plus bottle yielded positive results an average of 5.0 h earlier than the PF bottle for compliant clinically significant cultures (18.3 h versus 23.2 h, P = 0.004). PF Plus is an improved medium for detecting microorganisms that cause pediatric bloodstream infections.