An alternative approach in determining cause, treatment, and prevention of obesity is to study those who appear resistant to the obesogenic environment. We examined appetite responses in 33 obesity resistant individuals (ORI) versus 28 obesity susceptible individuals (OSI). Fingerprick blood samples to measure ghrelin, total peptide YY (PYY), leptin, glucose, and insulin along with appetite ratings were collected at baseline and 15, 30, 60, 120, and 180 min following consumption of a standardized meal. Fasting, area under the curve (AUC), peak/nadir, and time to peak/nadir were compared. Participants completed the three factor eating questionnaire (TFEQ). No significant differences were observed for ghrelin or PYY. Higher leptin concentrations in the OSI disappeared after controlling for percent body fat (%BF). Significant differences in appetite ratings included a lower hunger nadir among OSI compared with ORI (P = 0.017). Dietary restraint (P < 0.001) and disinhibition (P < 0.001) were lower in ORI compared with OSI, with and without adjustment for %BF. Given the differential body weight of the study groups, similar observed ghrelin concentrations were unexpected, perhaps indicating OSI and ORI respond differently to the same ghrelin concentration. Also ORI response to hunger appears different as they exhibit lower levels of dietary restraint and disinhibition compared with OSI.