Simple SummaryPrevious smaller studies have showed that a common heart medication, beta-blockers, potentially could reduce the risk of recurrence in patients with malignant melanoma and thereby increase survival. By combining different Swedish population-based registries, a total of 12,738 patients with melanoma were identified. Out of these patients 3702 had been prescribed beta-blockers and the remaining 9036 patients served as the control group. In a statistical analysis adjusting for known risk factors there was no effect of beta-blockers in reducing the risk of dying from melanoma. In conclusion, this population-based registry study could not verify the hypothesis that the use of beta blockers would improve survival in patients with melanoma.Previous studies have demonstrated an anti-tumoral effect of beta-adrenergic blocking agents on cutaneous melanoma (CM). The aim of this study was to investigate if beta-adrenergic blocking agents have an impact on survival in Swedish patients with melanoma. A population-based retrospective registry study including all patients diagnosed with a primary invasive melanoma between 2009 and 2013 was performed. Data from the Swedish Melanoma Register were linked to the Swedish Prescribed Drug Registry and the Swedish Cause of Death Register. Cox regression analyses including competing risk assessments were performed. There were 12,738 patients included, out of which 3702 were exposed to beta-blockers vs. 9036 non-exposed patients. Age, male sex, Breslow thickness, ulceration, and nodal status were independent negative prognostic factors for melanoma-specific survival (MSS). Adding beta-blockers to the analysis did not add any prognostic value to the model (HR 1.00, p = 0.98), neither when adjusting for competing risks (HR 0.97, p = 0.61). When specifically analyzing the use of non-selective beta-blockers, the results were still without statistical significance (HR 0.76, p = 0.21). In conclusion, this population-based registry study could not verify that the use of beta-adrenergic blocking agents improve survival in patients with melanoma.