Context A vast body of published literature examines and evaluates the properties of bone restorative materials in combination with other biomaterials or as stand-alone applications. If we exclude the studies investigating the effectiveness of regenerative therapy with enamel matrix derivative (EMD), in all other cases, bone regenerative materials are placed on a "pedestal." Therefore, the study we have initiated covers methods whose protocol does not use bone-repair materials. The clinical and radiographic results obtained are compared to determine which of these methods is the most reliable. The most important goal we set out was to determine if periodontal regenerative therapy would be effective without the use of bone graft restorative materials. Aim This study aimed to investigate, analyze, and compare the outcomes of four groups of patients with vertical bone defects (infrabony defects (IBDs)) who were treated using regenerative methods without the involvement of bone repair materials. Materials and methods Forty-eight cases that fulfilled all participation criteria for the study were selected. The O'Leary plaque index (PI) and Ainamo and Bay gingival index (GI) were assessed at the reassessment visit after the Hygiene Phase, the current periodontal status was recorded, and at least one IBD was identified. Cone beam computed tomography (CBCT) was ordered, and the size of each defect was measured by three parameters. In this study, all IBDs were randomly allocated to four groups. The first category encompasses IBDs, wherein regenerative therapy utilizing autogenous, platelet-rich plasma (PRP) is implemented. The second group comprises IBDs, which undergo regenerative therapy utilizing EMD. The third category encompasses IBDs in which guided tissue regeneration (GTR) is conducted using solely a barrier membrane. The fourth group encompasses IBDs, wherein GTR utilizing a barrier membrane and PRP took place. Six months after regenerative therapy, regardless of which of the four methods was used, all patients were reassessed clinically by CBCT. Statistical methods were used to evaluate, analyze, and compare the results in the four groups. Results A statistically significant decrease in the "probing pocket depth" indication, a statistically significant clinical attachment level gain, and a statistically significant decrease in the CBCT indicators "A" and "B" were observed in all four groups of patients under study. When it comes to the CBCT indicator "C," the results for each of the four groups of patients under study fall somewhere between statistical significance and non-significant. Conclusions Regardless of the regenerative therapy technique used, all patients under examination showed improvements in imaging and clinical markers. The four patient groups' results did not differ in any way that was statistically significant.