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We conducted a review of invasive early-onset neonatal group B Streptococcus (GBS) infections that occurred during 2000–2004 in Alaska to determine the proportion of cases that might have been prevented by complete implementation of the 2002 Centers for Disease Control and Prevention (CDC) guidelines.Cases were identified from statewide laboratory-based surveillance conducted by the CDC Arctic Investigations Program, and from the Alaska Medicaid database using International Classification of Diseases 9 codes 038.0, 041.02, 320.2, and 482.3. Neonates were considered to have early-onset disease if clinical illness within 6 days after birth was accompanied by GBS isolation from a normally sterile site. Maternal and neonatal medical records were reviewed. Potentially preventable cases were those for whom the 2002 CDC GBS maternal screening and intrapartum antimicrobial prophylaxis (IAP) guidelines were not completely implemented. Preventability of events not related to clinician implementation of the guidelines were not considered.Twenty-one neonates with invasive early-onset GBS disease were identified (0.42/1,000 live births). Three of the eight mothers for whom IAP was indicated, did not receive adequate IAP. Nine of the 13 mothers for whom there was no indication for IAP, had not been screened appropriately. Therefore, a total of 12 neonates were determined to have had potentially preventable GBS disease.Over 50% of the invasive early-onset neonatal GBS cases in Alaska were potentially preventable. The majority of these cases may have been prevented by closer adherence to either specific IAP administration guidelines or to maternal screening guidelines.