Both throat swabs and nasopharyngeal suction (NPS) specimens are used for microbiological assessment in non-sputum-producing patients with cystic fibrosis (CF), but studies comparing their diagnostic yield are lacking. We, therefore, conducted a prospective study in young CF patients, in which both techniques were performed in random order. Forty-seven consecutive CF children aged 6 months to 10 years were studied during routine visits to the clinic. CF relevant pathogens were found in the majority of patients with no significant differences in the rate of positive cultures for Staphylococcus aureus, Haemophilus influenzae, or Pseudomonas aeruginosa. A statistically significant difference was observed in the rate of detection of other organisms with only 9/47 (19%) of throat swab specimens and 27/47 (57%) of NPS specimens being positive (P = 0.0004). This included 12 positive cultures for Streptococcus pneumoniae and 11 cultures that were positive for Moraxella catarrhalis, both of which are frequent colonizers of the upper airway. Therefore, the most common bacterial pathogens affecting the CF lung appear to be detected in similar frequency by throat swab as by nasopharyngeal suction. There is evidence that nasopharyngeal suction yields more specimens of Streptococcus pneumoniae and Moraxella catarrhalis, which may reflect upper airway colonization rather than lower airway infection. We conclude that nasopharyngeal suction is not routinely warranted as there is no benefit over throat swab in detection of CF pathogens in infants and young children with CF.