Patients with cystic fibrosis perform airway clearance techniques and receive nebulized medications on a regular basis. Some positive expiratory pressure (PEP) devices allow concomitant administration of aerosol. I hypothesized that this practice alters the aerosol characteristics and patient dose. I compared the aerosol characteristics and patient dose of nebulized albuterol from 2 types of nebulizer, alone and when connected to different PEP and vibratory PEP devices.Three units of a continuous-output nebulizer (Up-Draft II Opti-Neb) and 3 units of a breath-enhanced nebulizer (LC Plus) were tested alone and connected to PEP devices (Acapella Choice, Acapella Duet, and EzPAP for Up-Draft II Opti-Neb, and Pari PEP at 2 different settings, and Pari PEP S system with the LC Plus). Aerosol characteristics were evaluated with a cooled cascade impaction technique. The nebulizers were loaded with 2.5 mg/3 mL albuterol solution and operated for 4 min at 6 L/min (wall air). Patient dose was evaluated with simulated breathing patterns for a child, small adult, and large adult. Albuterol was assayed via spectrophotometry.Connecting the LC Plus to the PEP devices did not change the aerosol characteristics or patient dose. Connecting the Up-Draft II Opti-Neb to the PEP devices significantly reduced the mass median aerodynamic diameter, from 4.13 μm to 3.72 μm with EzPAP (P = .02), 1.24 μm with Acapella Choice (P < .001), and 1.22 μm with Acapella Duet (P < .001). The total amount of albuterol captured by the impactor decreased when connected to either Acapella Choice (65%) or Acapella Duet (69%), with 17-25% retained in the PEP devices. Patient dose decreased by 76% and 84% when connected to Acapella Choice and Acapella Duet, respectively.Concomitant use of nebulizer and PEP or vibratory PEP devices that obstruct the aerosol pathway significantly decrease the aerosol particle size and the patient dose.