Minimal intervention is generally achieved by using direct composite resin (CR) restorations. However, deep caries lesions may lead to pulpal complications. This study evaluated the risk of endodontic complications after CR restoration in relation to depth of caries lesions. Data on 507 teeth from 316 adults treated with CR were analyzed. Caries depth was expressed as a percentage of the distance between the outer edge of the dental enamel and the pulp base on preoperative radiographs. The interval between CR restoration and follow-up root canal treatment was obtained from electronic treatment records for a period of 24 months. A Cox proportional hazards model was used to investigate the association between risk of endodontic complications and caries depth. Sixteen teeth (3.2%) required root canal treatment within 24 months. No root canal treatment was required after CR treatment for caries affecting <50% of the outer edge of enamel and pulp. As compared with CR treatment of caries lesions with a size of <80%, there was a significantly higher risk of root canal treatment for caries lesions with a size of 80% to 89% (hazard ratio, [95% CI]: 34.68 [4.23-284.11]) and ≥90% (92.01 [10.36-817.41], respectively).