Patients with hereditary α1‐proteinase inhibitor (α1‐PI) deficiency are at risk of developing lung emphysema. To prevent the development of this disease, α1‐PI replacement therapy via inhalation may be a more convenient and effective therapy than the intravenous administration of the drug. In order to optimise this treatment approach, lung deposition of inhaled radiolabelled α1‐PI (Prolastin®) was studied using four different commercial inhalation devices (PARI‐LC Star®, HaloLite®, and AKITA® system in combination with LC Star® and Sidestream®) in six patients with α1‐PI deficiency and mild-to-severe chronic obstructive pulmonary disease. The time required to deposit 50 mg of the Prolastin® (5% solution) in the lung periphery was used as a measure for the efficiency of delivery. The time was calculated from measurements of total and peripheral lung deposition of the radiolabelled α1‐PI. This time was shortest for the AKITA® system (18–24 min) and significantly higher for the PARI‐LC Star® (44 min) and the HaloLite® (100 min). The higher efficiency of drug delivery using the AKITA® system is due to the fact that this device controls breathing patterns, which are optimised for each patient individually.