Noncontained (1- or combined 1- to 2-wall) periodontal intraosseous defects represent challenging clinical situations with unpredictable surgical therapeutic outcomes. This randomized clinical trial assessed demineralized freeze-dried bone allograft (DFDBA) with low speed-platelet-rich fibrin (PRF) membrane compared to DFDBA with collagen membrane (CM) in the surgical periodontal therapy of noncontained intraosseous defects of stage III periodontitis patients. Twenty-two stage III periodontitis patients with noncontained intraosseous defects measuring ≥3 mm and clinical attachment loss ≥5 mm were randomly allocated into two groups: test group (low-speed PRF membrane + DFDBA) and control group (CM + DFDBA), with 11 participants per group. Clinical and radiographic assessments were conducted at baseline, 3, 6, 9, and 12 months for clinical attachment level (CAL; primary outcome), gingival recession depth (GRD), probing depth (PD), full mouth bleeding score (FMBS) and full mouth plaque score (FMPS), radiographic bone fill and radiographic linear defect depth (RLDD; all secondary outcomes). The mean (±SD) CAL-gain for the test group was 2.45 (±1.51), 2.91 (±1.70), 2.91 (±1.87), and 2.82 (±1.83) mm, while for the control group 2.82 (±1.25), 3.27 (±1.27), 3.00 (±1.41), and 2.64 (±1.50) mm at 3, 6, 9, and 12 months, respectively, with no significant intergroup differences ( > 0.05). Despite the absence of significant intergroup differences, both groups demonstrated significant intragroup improvement in CAL- and PD-gain, and RLDD-reduction at 3, 6, 9, and 12 months as well as RLDD improvement at 12 months ( < 0.05). PRF membranes, in conjunction with DFDBA, show significant improvement of periodontal clinical and radiographic parameters, comparable to CMs with DFDBA. ClinicalTrials.gov identifier: NCT03922503.