Purpose: This study evaluated the biologic effect in vivo of hydroxyapatite (HA) nanoparticle surface modification on commercially pure titanium or titanium alloy (Ti-6Al-4V) implants. Materials and Methods: Miniature cylindric titanium and Ti-6Al-4V implants were pretreated with dual acid etching (DAE), and a subset was further modified with HA nanoparticles using discrete crystalline deposition (DCD). The resultant implant surface topography was characterized by interferometry and scanning electron microscopy. Miniature implants of DAE titanium, DAE Ti-6Al-4V, DCD titanium, and DCD Ti-6Al-4V were surgically placed in the femora of rats. After 4 days, 1 week, and 2 weeks of healing, osseointegration was evaluated by implant push-in tests or microcomputed tomography (microCT). Ti-6Al-4V samples were harvested at week 2 and prepared for nondecalcified histology and subjected to bone-to-implant contact (BIC) measurement. Results: DCD treatment generated a complex surface morphology via the bonded HA nanoparticles. However, the amplitude and spatial, hybrid, and functional surface roughness parameters measured at the micron and submicron levels did not depict topographic differences between the DAE and the DCD-modified implants. DAE titanium and DAE Ti-6Al-4V implants showed a sharp increase in push-in values at week 1, followed by a plateau at week 2. DCD titanium and DCD Ti-6Al-4V implants showed similar sharp increases at week 1, but the push-in values continued to increase at week 2. The surrounding bone architecture evaluated by microCT and the BIC ratio did not correlate with the biomechanical implant osseointegration measurement. Conclusions: DCD-derived surface modification with HA nanoparticles on titanium and Ti-6Al-4V implants resulted in progressive osseointegration profiles that were distinctively different from those of DAE controls. Surrogate measurements such as surface roughness parameters and BIC did not predict the biologic effect of the DCD treatment. The data indicate that early osseointegration may be more sensitively regulated by nanoscale surface characteristics. Keywords: crystalline hydroxyapatite, nanosurface topography, nanotechnology, osseointegration, titanium alloy