This study developed an emulsion-solvent evaporation method for producing haloperidol-loaded PLGA nanoparticles with up to 2% (wt/wt. of polymer) drug content, in vitro release duration of over 13 days and less than 20% burst release. The free haloperidol is removed from the nanoparticle suspension using a novel solid phase extraction technique. This leads to a more accurate determination of drug incorporation efficiency than the typical washing methods. It was discovered that PLGA end groups have a strong influence on haloperidol incorporation efficiency and its release from PLGA nanoparticles. The hydroxyl-terminated PLGA (uncapped) nanoparticles have a drug incorporation efficiency of more than 30% as compared to only 10% with methyl-terminated PLGA (capped) nanoparticles. The in vitro release profile of nanoparticles with uncapped PLGA has a longer release period and a lower initial burst as compared to capped PLGA. By varying other processing and materials parameters, the size, haloperidol incorporation and haloperidol release of the haloperidol-loaded PLGA nanoparticles were controlled.