Due to its excellent osteoconductivity and bone replacement capability, calcium phosphate cement (CPC) has been used for dental and craniofacial repairs.  However, its low strength limits use to only non-stress procedures.  OBJECTIVES:  This study aimed to increase the strength of CPC while creating macropores for bone ingrowth.  METHODS:  Chitosan and mesh were incorporated into CPC.  The specimens were self-hardened in 3 mm x 4 mm x 25 mm molds, demolded after 4 h, immersed in a physiological solution for 1 d to 84 d, and tested in 3-point flexure.  The reinforcement mechanisms and macropore formation were examined with SEM.  RESULTS:  While CPC control failed catastrophically, the CPC reinforced with chitosan and mesh sustained extensive deformation without fracture. CPC control had a flexural strength (mean ± sd; n = 6) of (3.3 ± 0.4) MPa.  Chitosan or mesh increased the strength to (11.9 ± 0.8) MPa and (21.3 ± 2.7) MPa, respectively.  These values were significantly different from each other (Tukey's; fcc = 0.95).  When both chitosan and mesh were incorporated into CPC, the strength increased dramatically to (43.2 ± 4.1) MPa, and work-of-fracture was increased by two orders of magnitude.  After 84 d, mesh dissolution created highly-interconnected macropores.  The reinforced CPC scaffold had a strength 39% higher, and work-of-fracture 256% higher, than CPC control without macropores.  CONCLUSIONS:  The novel method of combining different reinforcement agents in the same material resulted in dramatic synergistic strengthening for CPC.  The interconnected macropores thus formed in CPC were suitable for vascular and new bone ingrowth.  These improved features may allow CPC to be used for the repair of larger, stress-bearing dental and craniofacial defects.  Supported by NIDCR R29 DE12476 and DE11789, NIST, and the ADAHF.