Abstract Background: β-Adrenergic receptor blockers have been associated with improved survival among patients with different types of malignancies, but available data for patients with non–small cell lung cancer (NSCLC) are contradictory and limited to small hospital-based studies. We therefore aimed to investigate whether β-blocker use at the time of cancer diagnosis is associated with lung cancer mortality in the largest general population-based cohort of patients with NSCLC to date. Methods: For this retrospectively defined nationwide cohort study, we used prospectively collected data from Swedish population and health registers. Through the Swedish Cancer Register, we identified 18,429 patients diagnosed with a primary NSCLC between 2006 and 2014 with follow-up to 2015. Cox regression was used to estimate the association between β-blocker use at time of cancer diagnosis ascertained from the Prescribed Drug Register and cancer-specific mortality identified from the Cause of Death Register. Results: Over a median follow-up of 10.2 months, 14,994 patients died (including 13,398 from lung cancer). Compared with nonuse, β-blocker use (predominantly prevalent use, 93%) was not associated with lung cancer mortality [HR (95% confidence interval): 1.01 (0.97–1.06)]. However, the possibility that diverging associations for specific β-blockers and some histopathologic subtypes exist cannot be excluded. Conclusions: In this nationwide cohort of patients with NSCLC, β-blocker use was not associated with lung cancer mortality when assessed in aggregate in the total cohort, but evidence for some β-blockers is less conclusive. Impact: Our results do not indicate that β-blocker use at lung cancer diagnosis reduces the cancer-specific mortality rate in patients with NSCLC.