Millimeter-sized hydroxyapatite (HA) single crystals were synthesized from chlorapatite (ClAp) crystals via the ionic exchange of Cl− for OH− at high temperature. X-ray diffraction, Fourier-transform infrared spectroscopy, and chloride content measurements were used to follow the progress of this conversion, and to assess the effect of the experimental conditions (temperature, time, and atmosphere). Cl−→OH− exchange took place homogeneously and was enhanced by firing in wet air. After firing at 1425°C for 2 h 92% of the Cl− ions were exchanged by OH− while maintaining crystal integrity. Temperatures above 1450°C damaged the surface of the crystals, destroying the hexagonal habit at 1500°C. The composition of these apatite crystals was close to bone mineral content. Their nanoindentation hardness (8.7 ± 1.0 GPa) and elastic nanoindentation modulus (120 ± 10 GPa) were similar to those of the starting ClAp (6.6 ± 1.5 GPa, and 110 ± 15 GPa, respectively). However, their average flexural strength was ~25% lower due to the formation of defects during the thermal treatments.