Different protocols and procedures for sinus lift and implant placement are available, generally involving the use of grafts to increase the tissue volume and/or prevent the Schneiderian membrane from collapsing. Among xenografts, deproteinised bovine bone graft (DBBP) is frequently used in sinus lift procedures. Leaving an ungrafted space following membrane elevation has proven to have a bony regenerative potential as well. This study aimed to compare the clinical and histological features of sinus lift surgery performed with or without biomaterials. Patients with severe maxillary posterior atrophy (residual bone height 2-6 mm and residual crest thickness ≥4 mm), and in need of sinus lift surgery to allow the placement of three implants were enrolled and randomly divided into two groups. They underwent sinus lifts with DBBP (control) or with a graftless technique (test) and immediate placement of two implants (a mesial and distal one). After 6 months, a bone sample was retrieved from the area between the previously inserted fixtures, and a third, central implant was placed. The collected bone samples were analyzed morphologically and histomorphometrically. The patients were provided with prosthetic restorations after 6 months and followed up for 5-12 years. Ten patients were enrolled in the test and nine in the control group. The 6-month follow-up showed in the control group an average augmentation of 10.31 mm (±2.12), while in the test group it was 8.5 mm (±1.41) and a success rate of 96.3% in the control and 86.7% in the test group (p > 0.05). The histological analysis evidenced the presence of new bone tissue surrounded by immature osteoid matrix in the test group, and a variable number of DBBP particles surrounded by an immature woven bone matrix in the control group. The results of the present trial indicate that, with residual bone height of 2-6 mm and residual crest thickness ≥4 mm, sinus lift surgery with or without biomaterials followed by implant restoration, produces similar clinical and histological outcomes.