Abstract Background Pulmonary involvement in individuals with transthyretin cardiac amyloidosis is unclear. The aim of this study was to quantify 99m Tc-hydroxy methylene diphosphonate (HMDP) lung retention in hereditary transthyretin (ATTRv) cardiac amyloidosis patients and to relate tracer uptake intensity to pulmonary function and aerobic capacity. Methods We prospectively enrolled 20 patients with biopsy-proven ATTRv cardiac amyloidosis and 20 control subjects. Cardiac involvement was confirmed by echocardiography and nuclear imaging using 99m Tc-HMDP. Semi-quantitative analysis of the heart, rib and lung retention was assessed using a simple region of interest technique. Pulmonary function was evaluation by the means of whole-body plethysmography, diffusing capacity of the lung for carbon monoxide, forced oscillation technique and cardiopulmonary exercise testing. Results Pulmonary tracer uptake estimated by lung to rib retention ratio was higher in ATTRv amyloidosis patients compared with control subjects: median 0.62 (0.55–0.69) vs 0.51 (0.46–0.60); p = 0.014. Analysis of relation between lung 99m Tc-HMDP retention and pulmonary function parameters shown statistically significant correlations with total lung volume (% predicted), lung reactance (X rs 5 Hz) and peak VO 2 , suggesting total lung capacity restriction impaired elastic properties of the lung and poor aerobic capacity. Conclusion Our study suggests that some grade of pulmonary retention of 99m Tc-HMDP may occur in patients with cardiac ATTRv amyloidosis, which can elicit deleterious effects on patient’s lung function and aerobic capacity.