Objectives: The present study evaluated the indentation depth, storage modulus and biocompatibility of an experimental endodontic putty designed for endodontic perforation repair and direct pulp-capping (NeoPutty). The results were compared with the properties associated with the commercially available EndoSequence BC RRM Putty (ES Putty). Methods: Indentation depth was measured by a profilometer following indentation with the 1/4 lb Gilmore needle. Elastic modulus was evaluated using a strain-controlled rheometer. The effects of eluents derived from these two putties were examined on the viability and proliferation of human dental pulp stem cells (hDPSCs) and human periodontal ligament fibroblasts (hPDLFs), before (1 st testing cycle) and after complete setting (2nd testing cycle). Results: The ES Putty became more difficult to ident and acquired a larger storage modulus after exposure to atmospheric moisture. Biocompatibility results indicated that both putties were relatively more cytotoxic than the bioinert Teflon negative control, but much less cytotoxic than the zinc oxide-eugenol cement negative control. NeoPutty was less cytotoxic than ES putty in the 1st testing cycle, particularly with hDPSCs. Both putties exhibited more favourable cytotoxicity profiles after complete setting. Conclusions: NeoPutty has a better window of maneuverability after exposure to atmospheric moisture. From an in vitro cytotoxicity perspective, the NeoPutty may be considered more biocompatible than ES putty. Clinical significance: The experimental NeoPutty is biocompatible and is capable of reducing the frustration of shortened shelf life when jar-stored endodontic putties are exposed to atmospheric moisture during repeated opening of the lid for clinical retrieval.