Background: Mortality due to idiopathic pulmonary fibrosis (IPF) has been reported to be increasing in Spain, although the temporal evolution and regional differences across autonomous communities have not been fully characterized.

Objective: To analyse national and regional age-adjusted IPF mortality trends in Spain from 1999 to 2021 and to identify changes in temporal patterns using Joinpoint regression.

Methods: Age-adjusted mortality rates per 100,000 inhabitants were obtained from the Statistical Portal of the Spanish Ministry of Health for men and women in Spain and its autonomous communities. Deaths coded under ICD-10 J84.112 were included. Joinpoint regression was performed to estimate Annual Percent Change (APC) and detect inflection points in mortality trends. Statistical significance was set at p < 0.05.

Results: National IPF mortality increased from 2.17/100,000 in 1999 to 2.85/100,000 in 2021. Two distinct phases were identified: an increase from 1999–2016 (APC 2.42%; 95% CI 1.8–3.0) followed by a decline from 2016–2021 (APC −2.83%; 95% CI −9.0 to 1.6). Men showed an increasing trend until 2016 (APC 2.40%), followed by an observed downward trend from 2016 to 2021 (APC −3.71%), although the confidence interval was wide and did not clearly exclude no change, while women exhibited a similar pattern (APC 1.45% to −3.97%) but with a more consistent decline after 2016. Regional trends varied substantially, with several communities displaying non-parallel trajectories compared with the national trend; only Baleares, Murcia and La Rioja experienced overall declines during the study period.

Conclusions: IPF mortality in Spain increased over the 22-year period but showed a likely downward trend that needs a prospective confirmation and marked regional heterogeneity. These findings underscore the need for continued monitoring and regional evaluation of IPF-related healthcare practices.