Purpose To determine the long-term prevalence and characteristics of acute hydrofluoric acid (HF) exposure in 2223 patients during the first 30 months after a mass-casualty exposure, and to confirm the antidotal effect of nebulized calcium on inhalation burns caused by HF. Methods This observational cohort study included patients after an HF spill in the Republic of Korea on September 27, 2012; registered patients were followed until April 2015. We assessed toxic effects, distance from spill, degree of acute poisoning, and the effect of nebulized calcium in HF-exposed individuals. Results Overall, 2223 patients received emergency management or antidote therapy for 20 days. Seventy-four of 134 patients with dermal toxicity received calcium–lidocaine gel, and 368 individuals with bronchial irritation signs received calcium gluconate via nebulizer nCG. A total 377 ampoules 786 g of calcium gluconate were used in the nCG formulation. Calcium administration did not cause adverse reactions during the observation period. Long-term cohort observation showed that 120 patients (120/2233, 5.4%) returned to medical facilities for management of HF-related symptoms within 1 month; 18 persons (18/1660, 1.1%) returned 1–3 months later with chronic cough and respiratory symptoms; and 3 patients (3/1660, 0.2%) underwent medical treatment due to upper-airway toxic symptoms more than 2 years after HF exposure. Conclusion Respiratory toxicity after mass exposure to an HF spill was successfully treated by calcium nebulizer. Based on our experience, detoxification processes and the amounts of antidote stocked are important when planning for future chemical disasters at the community level.