Purpose: To determine the prevalence of developmental defects of the enamel (DDE) in premolars whose infected predecessors were submitted to pulp therapy with antibiotic paste or extractions due to pulp necrosis. Materials and Methods: A cross-sectional study with a consecutive sample consisting of children and adolescents who presented with fully erupted premolars, was evaluated. Data were collected by dental examinations, in which the modified DDE index was applied. Dental records were evaluated and three groups of premolars were determined according to the clinical history of predecessors: GCTZ: with pulp necrosis and treated with CTZ (chloramphenicol, tetracycline, zinc oxide and eugenol) paste; GE: with pulp necrosis and treated by extraction; GH: healthy and physiologically exfoliated. Descriptive analysis and a logistic regression (p <0.05) were performed. Results: The study included 1017 premolars, DDE was present in 22.5%. Premolars belonging to the GE group presented higher odds of DDE (odds ratio (OR) = 3.52, 95% CI:2.29–5.40) than those of GCTZ group (OR = 2.43, 95% CI:1.51–3.91) and GH group (p <0.01). Enamel defects were more frequent in maxillary premolars (OR = 3.22, 95% CI:1.65–6.27, OR = 3.39, 95% CI:1.67–6.90, OR = 2.90, 95% CI:1.48–5.66 and OR = 3.10, 95% CI:1.54–6.23). Conclusions: The prevalence of enamel defects was higher in premolars whose predecessors were removed because of necrosis, followed by those treated with CTZ paste and those that were healthy by the time exfoliation occurred.