Oxytocin (OT) has been extensively studied with regard to its socio-cognitive and -behavioral effects. Its potential as a therapeutic agent is being discussed for a range of neuropsychiatric conditions. However, there is limited evidence of its effects on non-social cognition in general and decision-making in particular, despite the importance of these functions in neuropsychiatry. Using a crossover/within-subject, blinded, randomized design, we investigated for the first time if intranasal OT (24 IU) affects decision-making differently depending on outcome predictability/ambiguity in healthy males. The Iowa Gambling Task (IGT) and the Cambridge Risk Task (CRT) were used to assess decision-making under low outcome predictability/high ambiguity and under high outcome probability/low ambiguity, respectively. After administration of OT, subjects performed worse and exhibited riskier performance in the IGT (low outcome predictability/high ambiguity), whereas they made borderline-significant less risky decisions in the CRT (high outcome probability/low ambiguity) as compared to the control condition. Decision-making in healthy males may therefore be influenced by OT and adjusted as a function of contextual information, with implications for clinical trials investigating OT in neuropsychiatric conditions.