This paper presents the effect of process parameters of twin screw extruder and addition of Cloisite-15A on mechanical, thermal and moisture barrier properties of epoxy/Cloisite-15A nanocomposites. Four lobed kneading blocks were used the in shearing zone of the extruder, based on their effectiveness in dispersing nanofillers in epoxy. Screw speeds from 100 min(-1) to 400 min(-1), number of passes up to 15, temperature from 5 degrees C to 80 degrees C and Cloisite-15A contents from 1 wt.% to 2.5 wt.% were considered for designing the L-12 Orthogonal Array. Improvements in tensile strength, compression strength, flexural strength, impact strength, hardness and moisture diffusivity in the nanocomposites were 11.89%, 20.06%, 27.73%, 37.26%, 25.48% and 56.22% respectively, when compared to neat epoxy. The improvements were achieved for screw speed of 400 min(-1), 5 passes through the extruder, processing temperature of 5 degrees C and 2 wt.% of Cloisite-15A. Dispersion of Cloisite-15A in epoxy was studied by XRD, SEM and TEM. Thermal stability and moisture barrier properties were superior in the nanocomposites.