PURPOSE: To evaluate the effect of a solo ultraendurance open-water swim on autonomic and nonautonomic control of heart rate (HR). METHODS: A male athlete (age 48 y, height 172 cm, body mass 68 kg, BMI 23 kg/m2) underwent HR-variability (HRV) and circulating catecholamine evaluations at different times before and after an ultraendurance swim crossing the Adriatic Sea from Italy to Albania. HRV was measured in 5-min segments and quantified by time and frequency domain. Circulating catecholamines were estimated by salivary alpha-amylase (sAA) assay. RESULTS: The athlete completed 78.1 km in 23:44 h:min. After arrival, sAA levels had increased by 102.6%. Time- and frequency-domain HRV indexes decreased, as well (mean RR interval, -29,7%; standard deviation of normal mean RR interval, -63,1%; square root of mean squared successive differences between normal-to-normal RR intervals, -49.3%; total power, -74.3%; low frequency, -78.0%; high frequency, -76.4%), while HR increased by 41.8%. At 16-h recovery, sAA had returned to preevent values, while a stable tachycardia was accompanied by reduced HRV measures. CONCLUSION: To the authors\' knowledge, this is the first study reporting cardiac autonomic adjustments to an extreme and challenging ultraendurance open-water swim. The findings confirmed that the autonomic drives depend on exercise efforts. Since HRV changes did not mirror the catecholamine response 16 h postevent, the authors assume that the ultraendurance swim differently influenced cardiac function by both adaptive autonomic and nonautonomic patterns.