The Modified Minimally Invasive Surgical Technique (M-MIST) was designed to improve wound stability and reduce patient morbidity. This case series aimed to evaluate clinical outcomes of periodontal regenerative therapy using recombinant human fibroblast growth factor (rhFGF)-2 with M-MIST for the treatment of intrabony defects. Following initial periodontal therapy, nine intrabony defects in seven patients received rhFGF-2 therapy. Using M-MIST, a buccal incision was made to gain access to the defect without interdental and lingual incisions. After debridement, rhFGF-2 was applied to the defect. Periodontal parameters were evaluated at baseline and at 3, 6, and 12 months postoperatively. Composite Outcome Measure (COM) and patient-reported outcome measure (PROM, recorded using an oral health-related quality of life [QoL] instrument) were also used for evaluation. At 12 months postoperative, mean probing depth reduction was 4.2 ± 0.8 mm and clinical attachment gain was 4.7 ± 0.7 mm. The mean value for gingival recession was -0.3 ± 0.5 mm. According to COM, the outcomes of the treated sites were successful. An improvement in oral health-related QoL was noted at 12 months compared to after the initial periodontal therapy. This case series shows that rhFGF-2 therapy with M-MIST yields favorable clinical outcomes in the treatment of intrabony defects.