Abstract This study explored the role of situational temptation, a component of self-efficacy, in adolescent and young adult (ages 16-24) HIV medication adherence by assessing participants' perceptions of their temptation to miss medications in various situations (e.g., when medication causes physical side effects, when there is fear of disclosure of HIV status). Youth (n = 186; 83% African American) were participants in a multisite clinical trial examining the efficacy of a motivational intervention. Data were collected using computer-assisted personal interviewing. Youth believed the most tempting reasons or situations that might lead them to miss their HIV medications to be symptoms (if the medicine caused you to have other physical symptoms) and sick (if the medicine made you sick to your stomach or made you throw up or if it tasted bad), but these were not significantly associated with nonadherence. This suggests disconnection between youths' expectations of temptation and actual tempting situations associated with nonadherence. Situational temptations associated with nonadherence included lack of social support, needing a break from medications, and not seeing a need for medications. Interventions to improve adherence should consider perceptions of HIV medications, particularly the benefits of taking medications and expectations of physical symptoms. Interventionists and clinicians should consider situations that may tempt youth to miss doses of medication and help youth gain insight into these temptations. Emerging methods, such as Ecological Momentary Assessment (e.g., daily diaries, cell phone text messaging), may be useful in gaining insight into the day-to-day experience of youth living with HIV.