When the outcome is uncertain, one’s decision to invest can be influenced by the potential loss. Risky decisions are usually less likely when the stakes are high. Following failed investment, trying again with the added motivation to recover the original investment, will increase the overall stake. This is known as ‘escalation of commitment’. Drugs that affect catecholamine receptors can alter the way magnitude of anticipated outcomes affect brain activity and behaviour. Correspondingly, clinical evidence suggests a link between catecholaminergic stimulant use and pathological gambling, for which escalation of commitment is a defining feature. We tested for an effect of methylphenidate (MPH), a catecholaminergic stimulant, on the inhibiting effect of high stakes on persistent risky choice. In a double-blind study, 20 healthy female subjects received a 20mg oral dose of MPH while 20 matched controls received a placebo (PL). All subjects performed a task of double-or-nothing gambles after loss with varied stakes. As expected, subjects who received PL gambled less when stakes were high. Subjects who received MPH, however, maintained relatively high persistence across all stakes. We also found that a trait measure of reward-responsiveness correlated with a reduction of stake effects on persistent risky choices in the placebo group and across all subjects, but not in the MPH group alone. MPH and reward responsiveness can reduce the extent to which escalating stakes inhibit further risky investment. This finding improves our understanding of the effects of methylphenidate and the neurobiology of stake-effects on persistent risky choice.