This study was conducted to determine if culture confirmation is needed for a negative rapid antigen detection test. Data on 18,509 tests done in patients younger than 18 years old were reviewed. Of the 14,167 (76.5%) that were negative, 968 (6.8%) were associated with positive cultures. No significant seasonal variation was noted. Significant differences were found between hospital and pediatric practices in the percentage of patients with a negative rapid antigen detection test who actually had group A beta-hemolytic streptococcus (3.5% to 9.8%). This study supports the recommendation of culture confirmation of a negative rapid antigen detection test and validation of results within an individual practice if confirmatory cultures are not being performed. This study showed a high false-negative rate of the negative rapid antigen detection test and variation among hospital and pediatric practices for rates of positive culture after a negative rapid antigen detection test.