Objectives: This pilot study examined how Methylphenidate (MPH0.5mg/kg) affects appetite sensations, food reinforcement, energy intake (EI), macronutrient consumption, and weight-loss in youth and adults living with obesity, without ADHD. Methods: This study employed a randomized, double-blind, placebo-controlled design. Eleven participants aged 28±6.9 yrs. (4 M, 7 F) were randomized to receive either MPH (n=5) or placebo group (n=6) for 60 days. Participants’ appetite sensations (Visual Analogue Scale), relative-reinforcing value of food (computer task), EI and macronutrient consumption (ad libitum buffet), and anthropometric measurements (DEXA) were measured at baseline and 60 days. Results: Repeated measures ANOVA revealed group x time interactions for appetite sensations [desire to eat (p=0.01), hunger (p=0.002), and prospective food consumption (p=0.006)]; with greater reductions in MPH group compared to placebo. For the sense of fullness, there was an interaction between group and time (p=0.01), with a greater increase for MPH compared to placebo. Body weight significantly decreased in both groups (p=0.01), with a moderate to large effect size favouring the MPH group (-2.66 kg vs. – 1.16 kg, Cohen’s d =0.76). Changes between MPH and placebo did not differ significantly on EI, macronutrient consumption, or food reinforcement. Conclusions: Our data indicate for the first time that MPH suppresses appetite in individuals with obesity resulting in a moderate–sized effect on weight loss in the short-term. These findings warrant a larger trial to more definitively examine the effect that MPH has on weight loss and maintenance of weight loss, thereby evaluating its potential as a novel pharmacological agent in the management of obesity.