The objective of the study was to investigate the effect of positive expiratory pressure (PEP) and Flutter on expectoration in cystic fibrosis (CF) patients. Data was gathered through 260 treatments with 10 patients (5 female; 19.2 years; BMI: 18.0). Two methods were used alternately, first the patients started with Flutter and proceeded with PEP, and the next occasion they exercised in the reverse order, starting with PEP then continuing with Flutter. During each phase, 5 sets of 10 exhalations were performed. Sputum weight was measured after the use of the first device, and at the end of the treatment. During sessions starting with Flutter 4.0 ± 4.0 g sputum was expectorated, continuing with PEP, an additional 5.2 ± 5.0 g was produced, altogether 9.2 ± 8.2 g. At sessions starting with PEP 7.4 ± 3.7 g was expectorated, continuing with Flutter an additional 0.8 ± 1.4 g, that is 8.2 ± 4.1 g. Comparing the two devices by themselves, PEP proved to be significantly more efficient then Flutter. Comparing the two treatment types it is statistically not proven, which one is preferable using both devices. Conclusively, PEP is significantly more efficient than the Flutter in sputum expectoration among CF patients. The Flutter is a useful supplementary device.