OBJECTIVE: Inpatient discharge education is often suboptimal. Measures of parents' perceived comprehension of discharge instructions are included in national metrics given linkage to morbidity; few studies compare parents' perceived and actual comprehension. We 1) compared parent perceived and actual comprehension of discharge instructions and 2) assessed associations between plan complexity and parent health literacy with overestimation of comprehension (perceive comprehension but lack actual comprehension). METHODS: Prospective cohort study of English/Spanish-speaking parents (n = 192) of inpatients ≤12 years old and discharged on ≥1 daily medication from an urban public hospital. We used McNemar's tests to compare parent perceived (agree/strongly agree on 5-point Likert scale) and actual comprehension (concordance of parent report with medical record) of instructions (domains: medications, appointments, return precautions, and restrictions). Generalized estimating equations were performed to assess associations between low parent health literacy (Newest Vital Sign score ≤3) and plan complexity with overestimation of comprehension. RESULTS: Medication side effects were the domain with lowest perceived comprehension (80%), while >95% of parents perceived comprehension for other domains. Actual comprehension varied by domain (41%-87%) and was lower than perceived comprehension. Most (84%) parents overestimated comprehension in ≥1 domain. Plan complexity (adjusted odds ratio 3.6; 95% confidence interval 2.9-4.7) and low health literacy (adjusted odds ratio 1.9; 1.3-2.6) were associated with overestimation of comprehension. CONCLUSIONS: Parental perceived comprehension of discharge instructions overestimated actual comprehension in most domains. Plan complexity and low health literacy were associated with overestimation of comprehension. Future interventions should incorporate assessment of actual comprehension and standardization of discharge instructions.