This study assessed the pulp healing response to human freeze-dried bone (FDB) in two cynomolgus monkeys using 36 noncarious primary teeth pulpotomized and randomly assigned to three medicaments. FDB was applied on the pulp stumps and covered with sterile tin foil as experimental group. The two other groups received either calcium hydroxide [Ca(OH)2], or IRM (reinforced ZOE). All teeth were restored with amalgam. One animal was sacrificed at 6 weeks and the other 6 months after treatment. Teeth were extracted and placed in 10% formalin. Histological evaluation indicated that 100% of teeth treated with FDB had vital pulps compared with 75% of the Ca(OH)2 group after 6 weeks. Dentin bridges were present in 87.5% of FDB versus 75% of Ca(OH)2 group. Inflammatory cells were absent or mild in 100% of FDB-treated versus 75% of the Ca(OH)2 group. After 6 months, 83.3% of FDB-treated teeth had vital pulps compared with the Ca(OH)2 group, which showed 100% pulpal necrosis. In FDB-treated pulps, 100% of teeth showed dentin bridges versus 50% of teeth treated with Ca(OH)2. Inflammatory cells were absent or mildly present in 83.3% of FDB-treated teeth while 100% of Ca(OH)2 showed moderate to severe inflammation. IRM-treated teeth all showed pulpal necrosis after 6 months. We concluded that FDB was superior to calcium hydroxide in treating primary pulp dentition in cynomolgus monkeys.