SYNOPSIS Objective. To experimentally test whether perceptions of cry stimuli and autonomic nervous system reactivity help to explain parenting self-efficacy (PSE). Design. First-time pregnant women (N = 151) completed a task during which they responded to infant cries. After each cry, they received performance feedback, which was manipulated to simulate an easy-to-soothe (80% success) and a difficult-to-soothe (20% success) infant. After responding to each infant, participants rated cry perception and PSE. Using continuous ambulatory recording, changes in heart rate, skin conductance level, pre-ejection period, and respiratory sinus arrhythmia were compared across conditions. Results. An increase in PSE followed the easy-to-soothe infant, whereas a decrease in PSE occurred after the difficult-to-soothe infant. These changes in PSE were not associated with autonomic reactivity during the task. Women with more negative perceptions of the cries had larger decreases in PSE during the task. Perceiving the difficult-to-soothe infant more negatively than the easy-to-soothe infant was related to larger decreases in PSE after the second series of cries. Conclusion. Negative cry perceptions were related to decreasing PSE. Negative perceptions of parenting duties may increase the saliency of parents’ successes and failures. These findings are relevant to further testing mechanisms of change in PSE as well as the design of interventions to augment PSE.