Background: Recent studies have suggested that transthyretin amyloidosis (ATTR) is a more common cause of heart failure (HF) than previously appreciated, and novel treatments for amyloidosis are emerging. About one-half of patients with ATTR cardiac amyloidosis have a history of carpal tunnel syndrome (CTS). Objectives: This study examined the risk of amyloidosis, HF, and other adverse cardiovascular outcomes associated with CTS relative to control subjects without CTS. Methods: Using Danish nationwide registries from 1996 to 2012, 56,032 patients were identified who underwent surgical treatment for CTS, and they were compared with a sex- and age-matched cohort (ratio 1:1) from the general population to examine their risk of amyloidosis, HF, and other adverse cardiovascular outcomes. Cumulative incidence curves and Cox proportional hazard models were used to assess differences. Results: As expected, CTS was associated with a future diagnosis of amyloidosis (hazard ratio: 12.12 [95% confidence interval: 4.37 to 33.60]). CTS was associated with a higher incidence of HF, and this held true in the adjusted analysis yielding a hazard ratio of 1.54 (95% confidence interval: 1.45 to 1.64). No significant interaction with sex was found (p = 0.5). Risk of other adverse outcomes was also associated with CTS (p < 0.0001 for atrial fibrillation, atrioventricular heart block, and pacemaker implantation). Conclusions: Patients who undergo surgical treatment for CTS are associated with a higher risk of amyloidosis and HF relative to matched control subjects from the general population. Other cardiovascular outcomes were also increased with CTS.