The precipitation technique was used to prepare non-polymeric alendronate nanoparticles. The influence of various formulation parameters on the average particle size was investigated and the effect of various stabilizers (PVA, tween, chitosan, alginate, PEG, HPMC, poloxomers) was evaluated. The selection of surfactant was a key factor to produce particles with desired properties. Poloxomer F68 was found best in achieving the minimum particle size and providing physical stability to the drug. On basis of preliminary trials, a central composite design was employed to study the effect of independent variables, drug concentration (X-1), antisolvent volume (X-2), stirring speed (X-3), and stabilizer concentration (X-4) on the average particle size. The drug and stabilizer concentrations exhibited a more significant effect on a dependent variable. The particle size varied from 62 to 803.3 nm depending upon the significant terms. The validation of optimization study, performed using six confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error (+/- SD) as -2.32 +/- 2.47. The minimum particle size (44.11 nm) was predicted at 10 mg/ml drug concentration, 20 ml antisolvent volume, 925 rpm stirring speed, and 8.5% stabilizer concentration with 98.16% experimental validity. Respirable fraction for optimized nanosized alendronate (43.85% +/- 0.52%) was significantly higher when compared with commercial alendronate (17.6 +/- 0.32). Mass median aerodynamic diameter of designed particles was 3.45 mm with geometric standard deviation of 2.10.