BackgroundIdiopathic pulmonary fibrosis (IPF) is a debilitating condition with significant morbidity and poor survival. Since 2010, there has been increased activity in the development of treatments that aim to delay progression of the disease.ObjectiveOur study involves a comprehensive review of the literature for evidence on health-related quality of life (HRQoL), healthcare resource use (HCRU) and costs, and an assessment of the burden of illness of the condition.MethodsWe carried out a systematic literature review (SLR) to identify economic evaluations and HRQoL studies. We searched EMBASE, MEDLINE and MEDLINE In Process for relevant studies from database origins to April 2017. Alongside the presentation of the study characteristics and the available evidence, we carried out a qualitative comparison using reference population estimates for HRQoL and national health expenditure for costs.ResultsOur search identified a total of 3241 records. After removing duplicates and not relevant articles, we analysed 124 publications referring to 88 studies published between 2000 and 2017. Sixty studies were HRQoL and 28 were studies on costs or HCRU. We observed an exponential growth of publications in the last 3–5 years, with the majority of the studies conducted in Europe and North America. Among the HRQoL studies, and despite regional differences, there was some agreement between estimates on the absolute and relative level of HRQoL for patients with IPF compared with the general population. Regarding costs, after adjustments for the cost years and currency, the suggested annual per capita cost of patients with IPF in North America was estimated around US$20,000, 2.5–3.5 times higher than the national healthcare expenditure. Additionally, studies that analysed patients with IPF alongside a matched control cohort suggested a significant increase in resource use and cost.ConclusionThe reviewed evidence indicates that IPF has considerable impact on HRQoL, relative to the general population levels. Furthermore, in studies of cost and resource use, most estimates of the burden were consistent in suggesting an excess cost for patients with IPF compared with a control cohort or the national health expenditure. This confirms IPF as a growing threat for public health worldwide, with considerable impact to the patients and healthcare providers.Electronic supplementary materialThe online version of this article (10.1007/s40273-018-0631-8) contains supplementary material, which is available to authorized users.