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Severe heart failure (HF) is often associated with cachexia that reverses post-heart transplantation (HTx) with frequent development of obesity. Ghrelin is a novel appetite-stimulating hormone. The aim was to determine the role of ghrelin in regulating appetite, food intake, and body composition in HF and post-HTx.We measured serial ghrelin, hunger sensation, caloric intake, and body composition in 12 HF patients awaiting HTx, 12 patients 12.7 ± 8.6 months post-HTx, and 7 controls. Seven of 12 HF patients were followed for longitudinal analysis post-HTx. Body mass index was 23.1 ± 3.1 in HF and 31.5 ± 5.5 post-HTx (P < 0.001). Heart transplantation patients had gained 18.0 ± 7.7 kg since HTx. Ghrelin area under the curve between controlled meals (control: 186 ± 39; HF: 264 ± 71; HTx: 194 ± 47 ng min/mL, P < 0.007) was higher in HF, but test meal caloric intake (control: 1185 ± 650; HF: 391 ± 103; HTx: 831 ± 309 kcal, P < 0.008) was lower in HF. The longitudinal analysis confirmed these findings.Heart failure may be associated with resistance to the appetite-stimulating effects of ghrelin, which may contribute to cachexia. Heart transplantation may be associated with resolution of ghrelin resistance, which may contribute to weight gain. These findings are preliminary and should be confirmed in larger trials.