Objective To compare the effects of acyl ghrelin (AG) and desacyl ghrelin (DAG) on blood pressure (BP), heart rate (HR), and other autonomic parameters in healthy humans and to elucidate hormonal mechanisms through which AG could exert cardiovascular (CV) effects. Design 17 healthy participants underwent frequent monitoring of systolic (sBP) and diastolic blood pressure (dBP), HR, respiratory rate (RR), and body surface temperature (Temp) during continuous infusion of AG, DAG, combined AG+DAG, or saline control before and during an IV-glucose tolerance test on 4 separate days. Plasma catecholamines, renin, and aldosterone levels were also measured. Differences in outcome measures between treatment groups were assessed using mixed model analysis. Results Compared to the saline control, AG and combined AG+DAG infusions decreased sBP, dBP, mean arterial blood pressure (MAP), HR, and Temp. In contrast, DAG infusion did not alter BP, RR, or Temp, but did decrease HR. The AG and AG+DAG infusions also raised plasma aldosterone levels compared to saline (p < 0.001) without affecting renin or catecholamine levels. Conclusions The decrease in BP, HR, RR, and Temp with AG infusion suggests mediation through the autonomic nervous system. The lack of response to DAG suggests that these autonomic effects require activation of the ghrelin receptor.