Porous and bioactive polyetheretherketone (PEEK) scaffolds have potential to replace metallic scaffolds for biologic fixation of permanent implants adjacent to trabecular bone, such as interbody spinal fusion devices. The objective of this study was to investigate the effects of the mold temperature and PEEK powder on the mechanical properties and crystallinity of hydroxyapatite (HA) whisker-reinforced PEEK scaffolds prepared using compression molding and porogen leaching. Scaffolds were prepared at mold temperatures ranging 340–390°C with a 50 or 10 μm PEEK powder, 75 vol% porosity, and 20 vol% HA whiskers. Scaffold mechanical properties were evaluated in unconfined, uniaxial compression and the PEEK matrix crystallinity was measured using specular reflectance Fourier transform infrared spectroscopy. Increased mold temperature resulted in increased compressive modulus, yield strength, and yield strain, reaching a plateau at ∼370°C. HA reinforcements were observed to be segregated between PEEK particles, which inhibited PEEK particle coalescence during compression molding at temperatures less than 365°C but also ensured that bioactive HA reinforcements were exposed on scaffold strut surfaces. Increased mold temperature also resulted in decreased PEEK crystallinity, particularly for scaffolds molded at greater than 375°C. The PEEK powder size exhibited relatively minor effects on the scaffold mechanical properties and PEEK crystallinity. Therefore, the results of this study suggested that HA-reinforced PEEK scaffolds should be compression molded at 370–375°C. The apparent compressive modulus, yield strength, and yield strain for scaffolds molded at 370–375°C was 75–92 MPa, 2.0–2.2 MPa, and 2.5–3.6%, respectively, which was within the range exhibited by human vertebral trabecular bone. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.