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Severe idiopathic pulmonary fibrosis is associated with an increased risk of cardiovascular disease and gastro-oesophageal reflux, which may influence prognosis. We evaluated associations between cardiovascular and antacid medications, and mortality, in oxygen-dependent pulmonary fibrosis (PF) of unknown cause.Prospective population-based study of adults starting long-term oxygen therapy (LTOT) for PF in Sweden 2005–2009. PF of unknown cause was defined by excluding patients with known or probable secondary PF. Time-dependent associations between medications and all-cause mortality were analysed using extended Cox regression, adjusting for potential confounders including age, sex, vital capacity, blood gases, body mass index, performance status, comorbidity and concurrent medications.Of 462 included patients, 329 (71%) died under observation. No patient was lost to follow-up. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) were associated with reduced adjusted mortality (HR 0.63; 0.47–0.85) and antiplatelet drugs with increased mortality (HR 1.49; 1.11–2.00), largely driven by higher mortality in women. There were no associations with mortality for antacid treatments,β-blockers, diuretics or statins.In oxygen-dependent PF, treatment with ACEI/ARB was associated with improved survival, antiplatelet drugs with decreased survival, whereas there was no association between antacid,β-blocker, diuretic or statin treatment and survival.This is a longitudinal study of cardiovascular and antacid treatments and mortality in oxygen-dependent pulmonary fibrosis. Adjusting for potential confounders, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) were associated with reduced mortality, antiplatelet drugs with increased mortality, whereas no association was found for antacid treatments, β-blockers, diuretics or statins.