© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.Objectives: The aim of this randomized, controlled, three-arm parallel group, and double-blinded clinical trial was to evaluate the clinical, radiographic, and histopathological success of three different pulp-capping materials in one-stage indirect pulp treatment of primary teeth. Materials and methods: The study included a total of 109 patients aged 5–9 years who had primary teeth with deep carious lesions and symptoms of reversible pulpitis. The teeth were divided into three groups according to the pulp-capping agents: (I) hard-setting calcium hydroxide (Dycal) (control group) (n = 36), (II) bioactive tricalcium silicate (Biodentine) (n = 37), and (III) resin-based tricalcium silicate (TheraCal LC) (n = 36). All the teeth were evaluated clinically and radiographically at 6, 12, 18, and 24 months postoperatively. A total of 23 primary mandibular second molars that were in their regular exfoliation period (24–40 months) were extracted and fixed in 10% formaldehyde solution. The specimens were evaluated histologically to assess the integrity of the odontoblastic layer, tertiary dentin formation quality of the dentin formed, severity of pulpitis, and other pulpal changes. Data were analyzed using Fisher’s exact test, Pearson’s chi-square test, and McNemar’s test (p = 0.05). Results: At the end of the 24-month follow-up period, the clinical and radiographic success rates for Dycal, Biodentine, and TheraCal LC were 100%, 100%, and 93.3%, respectively, and there was no significant difference among the groups (p > 0.05). However, the TheraCal LC group was statistically unsuccessful when compared to the other groups with regard to the integrity of the odontoblastic layer, severity of pulpitis, and other pulpal changes in histological examination (p < 0.05). Conclusion: Indirect pulp capping exhibited high clinical and radiographic success rates in the treatment of primary teeth regardless of the chosen pulp-capping agent. However, histological examination indicated that the pulp status was affected by the chosen capping material especially when selecting a resin-containing material such as TheraCal LC. Clinical relevance: Resin-free calcium silicate-based materials appear to be more favorable in the indirect pulp treatment of primary teeth, particularly in young-age groups that require long-term success.