Background: Endobronchial valve (EBV) placement is an established lung volume reduction procedure aiming to improve lung function and exercise capacity in patients with severe emphysema. As EBVs consist of silicone and nitinol (a metal alloy of nickel and titanium), there are concerns that nickel ions might be released and could have a clinical impact in patients with a contact allergy to nickel. Based on a case with hypersensitivity pneumonitis (HP) after treatment with EBVs, we aimed to evaluate the in vitro nickel release from EBVs using inductively coupled plasma mass spectrometry (ICP-MS) and scanning electron microscopy (SEM). Methods: Six EBVs were immersed in artificial saliva for a period of 7 days. At 24-h intervals, the nickel ion concentration was measured using ICP-MS. Results: There was evidence of a significant nickel release from EBV during the first 48 h, which is possibly due to an incomplete silicone layer detected by SEM. The concentration of released nickel was below the toxic limit. Conclusions: To the best of our knowledge, we report the first case of HP after EBV treatment. Our finding of in vitro release of nickel ions from EBVs may contribute to the current understanding on hypersensitivity reactions after nitinol implants in patients with nickel contact allergy. However, it did not confirm a causative relationship.