The role of craving in opioid use disorder (OUD) has been well established with respect to heroin but less so with prescription opioids. This pilot study, conducted in 18 treatment-seeking patients with prescription OUD and 18 healthy volunteers, assessed spontaneous (in the moment) and cue-induced craving and their relationship to depression and anxiety. Patients (vs. healthy volunteers) exhibited increased spontaneous craving for prescription opioids. Relative to brief (10 s) random presentations of neutral and affective images, presented drug (prescription opioids) images elicited greater craving ratings in patients and were associated with higher valence and arousal ratings. Elevated depression and anxiety observed in patients (vs. healthy volunteers) were positively associated with spontaneous and cue-induced cravings. These findings tentatively support a role for drug craving and mental health comorbidity in prescription OUD and underscore the need for additional research to understand their causal relationships and their interactive dynamics during treatment and recurrence. (PsycInfo Database Record (c) 2025 APA, all rights reserved).