Purpose The single-flap approach (SFA) is a minimally invasive technique with limited mucoperiosteal flap elevation to gain access to the buccal/palatal aspects, thus limiting post-surgical complications. The purpose of the present study was to gain insights into the impact of the SFA over the double-flap approach (DFA) on periodontal flap treatment outcomes and patient compliance in terms of discomfort and time taken for surgical procedures. Methods Twenty patients with persistent probing pocket depths of ≥5 mm were scheduled for the SFA (test site) and for the DFA (control site). All the clinical periodontal parameters were recorded at baseline, 3 months, and 6 months. Radiographic bone level (cone-beam computed tomography) was evaluated at baseline and 6 months. Patients' postoperative pain perception and wound healing were also assessed. Results The SFA showed a significant reduction in periodontal pocket depth, gain in clinical attachment level (CAL), and gain in bone level when compared with the DFA. The SFA substantially improved wound healing and induced less postoperative pain than the DFA. Conclusions The SFA resulted in substantial improvement in the composite outcome measures, as shown by a reduction in pocket depth with minimal gingival recession, gain in CAL, early wound healing, less postoperative discomfort, and better patient-centered outcomes. Trial Registration Clinical Trials Registry-India Identifier: CTRI/2018/05/013562