Background: Tissue engineering represents a promising field in regenerative medicine, with bioresorbable polymers such as polycaprolactone (PCL) playing a crucial role as scaffolds. These scaffolds support the growth and repair of tissues by mimicking the extracellular matrix. Objective: This study aimed to assess the in vivo performance of three-dimensional PCL scaffolds by evaluating their effects on bone repair in rat calvaria and the tissue reaction in subcutaneous implant sites, as well as their impact on major organs such as the kidneys, lungs, and liver. Methods: Three-dimensional scaffolds made of PCL were implanted in the subcutaneous tissue of rats’ backs and calvaria. Histological analyses were conducted to observe the bone repair process in calvaria and the tissue response in subcutaneous implant sites. Additionally, the kidneys, lungs, and livers of the animals were examined for any adverse tissue alterations. Results: The histological analysis of the bone repair in calvaria revealed newly formed bone growing towards the center of the defects. In subcutaneous tissues, a thin fibrous capsule with collagenous fibers enveloping the implant was observed in all animals, indicating a positive tissue response. Importantly, no harmful alterations or signs of inflammation, hyperplasia, metaplasia, dysplasia, or hemorrhage were detected in the kidneys, lungs, and liver. Conclusions: The findings demonstrate that PCL scaffolds produced through additive manufacturing are biocompatible, non-cytotoxic, and bioresorbable, promoting osteoconduction without adverse effects on major organs. Hence, PCL is confirmed as a suitable biomaterial for further studies in tissue engineering and regenerative medicine.