Aim: This multicenter cross-sectional study evaluated the prevalence and variables statistically associated with primary and post-treatment apical periodontitis (AP) in subjects from eight Hispanic American countries. Methodology: Digital panoramic radiographs from subjects living in Argentina, Colombia, Ecuador, Guatemala, Mexico, Dominican Republic, Uruguay and Venezuela were analyzed. Teeth were evaluated for diverse factors, including the periapical status and presence of root canal treatment, caries, coronal restoration, intraradicular post, root resorption and periodontal involvement. Quality of root canal treatment and coronal restorations was also recorded. Associations between these diverse variables and AP were evaluated using chi-square tests and multivariable mixed-effects logistic regression with a random intercept for patient to account for within-patient clustering of teeth. Results: Overall, 11 850 subjects (294 662 teeth) were included; 51.5% of the subjects and 5.5% of the examined teeth had AP. Ecuador (62%) and Argentina (61%) had the highest AP prevalence per subject, whereas Mexico had the lowest (37%). Intermediate values were observed in Venezuela (57%), Guatemala (57%), Colombia (47%), Dominican Republic (46%) and Uruguay (45%). In general, 43% of the subjects had at least one root canal–treated tooth. Primary and post-treatment AP were observed in 3% and 42% of the teeth, respectively. Of the teeth with primary AP, 51% showed coronal restorations, and 32% had caries. Post-treatment AP was significantly associated with inadequate root canal fillings, inadequate coronal restorations and inadequate intraradicular posts (p < 0.05). Conclusions: The prevalence of AP in the Hispanic American countries evaluated was high, affecting nearly half of the population. Post-treatment AP was highly prevalent and predominantly linked to inadequate root canal fillings, deficient or absent.