Background: This study presents the Monte Carlo N-Particles Transport Code, Extension (MCNPX) simulation of proton dose distributions in a water phantom. Methods:In this study, fluence and dose distributions from an incident proton pencil beam were calculated as a function of depth in a water phantom. Moreover, lateral dose distributions were also studied to understand the deviation among different MC simulations and the pencil beam algorithm. MCNPX codes were used to model the transport and interactions of particles in the water phantom using its built-in "repeated structures" feature. Mesh Tally was used in which the track lengths were distributed in a defined cell and then converted into doses and fluences. Two different scenarios were studied including a proton equilibrium case and a proton disequilibrium case. Results:For the proton equilibrium case, proton fluence and dose in depths beyond the Bragg peak were slightly perturbed by the choice of the simulated particle types. The dose from secondary particles was about three orders smaller, but its simulation consumed significant computing time. This suggests that the simulation of secondary particles may only be necessary for radiation safety issues for proton therapy. For the proton disequilibrium case, the impacts of different multiple Coulomb scattering (MCS) models were studied. Depth dose distributions of a 70 MeV proton pencil beam in a water phantom obtained from MCNPX, Geometry and Track, version 4, and the pencil beam algorithm showed significant deviations between each other, because of different MCS models used. Conclusions: Careful modelling of MCS is necessary when proton disequilibrium exists.( Biomed J 2015;38:414-420)