In this paper, we demonstrate for the first time that the new class of fluoride-based inorganic upconverting nanoparticles, NaYF4:Er 3+, Yb3+, are the most efficient multiphoton excited fluorescent nanoparticles developed to date. The near-infrared-to-visible conversion efficiency of the aforementioned nanoparticles surpasses that of CdSe quantum dots and gold nanorods, which are the commercially available inorganic fluorescent nanoprobes presently used for multiphoton fluorescence bioimaging. The results presented here open new perspectives for the implementation of fluorescence tomography by multiphoton fluorescence imaging. © 2010 Optical Society of America.