Purpose: The aim of the present study was to compare the histomorphometrically evaluated new bone formation (NB), the radiographically measured graft stability, and the clinical implant outcome for maxillary sinus augmentation grafted with deproteinized bovine bone mineral (DBBM) with either small (Bio-Oss-S, Geistlich) or large (Bio-Oss-L, Geistlich) particles. Materials and Methods: Using a split-mouth study design, bilateral maxillary sinus augmentation was performed in 13 patients either with Bio-Oss-S particles (0.25 to 1 mm) or Bio-Oss-L particles (1 to 2 mm). After a healing period of 6 months, bone biopsies were axially retrieved in the molar region for histologic/histomorphometric analysis of NB, including subsequent staged implant placement. To determine graft stability, the maxillary sinus augmentation vertical graft heights were radiographically measured immediately after sinus augmentation, at implant placement, and at the 2- and 4-year post-augmentation follow-ups. In addition, the clinical implant-prosthodontic outcome (survival/ success/marginal bone loss) was assessed at 1 and 3 years post-loading. Results: A total of 22 sinuses from 11 patients with split-mouth evaluation were ultimately available for data and statistical analysis. Histomorphometric analysis of the axially retrieved bone biopsies revealed the presence of NB (S: 25.5% ± 7.0% vs L: 23.6% ± 11.9%; P = .640), residual graft particles (S: 19.6% ± 9.2% vs L: 17.5% ± 6.3%; P = .365) as well as connective tissue (S: 54.9% ± 9.2% vs L: 58.9% ± 12.5%; P = .283), without significant differences between the use of small (Bio-Oss-S) and large (Bio-Oss-L) particles. However, there was significantly (P = .021) higher bone-to-graft contact (BGC) for the small-particle graft sites (27.9% ± 14.8%) compared to the large-particle graft sites (19.9% ± 12.9%), representing a significantly higher osteoconductivity. Both particle sizes showed significant (P < .01) vertical graft height reduction over time (4 years) of about 10%, with predominant graft reduction in the time period between sinus augmentation and implant placement compared to any follow-up periods after implant placement. At the 3-year post-loading implant evaluation, all implants and prostheses survived (100%), and the peri-implant marginal bone loss (S: 0.52 ± 0.19 mm; L: 0.48 ± 0.15 mm) as well as the peri-implant health conditions (S: 87.5%, L:81.2%) did not differ between implants inserted with the two different xenograft particles used. Conclusions: The use of small and large bovine xenograft particles for maxillary sinus augmentation provides for comparable bone formation, ensuring stable graft dimensions combined with high implant success and healthy peri-implant conditions. However, small particle size resulted in a higher BGC, providing for higher osteoconductivity than with the larger particle size.