Thermostability of proteins in general and especially thermophilic proteins has been subject of a wide variety of studies based on theoretical and experimental investigation. Thermostability seems to be a property obtained through many minor structural modifications rather than certain amino acids substitution. In comparison with its mesophile homologue in a thermostable protein, usually a number of amino acids are exchanged. A wide variety of theoretical studies are based on comparative investigation of thermophilic proteins characteristics with their mesophilic counterparts in order to reveal their sequences, structural differences and consequently, to relate these observed differences to the thermostability properties. In this work we have compared a dataset of thermophilic proteins with their mesophilic homologues and furthermore, a mesophilic proteins dataset was also compared with its mesophilic homologue. This strategy enabled us first, to eliminate noise or background differences from signals and moreover, the important factors which were related to the thermostability were recognized too. Our results reveal that thermophilic and mesophilic proteins have both similar polar and nonpolar contribution to the surface area and compactness. On the other hand, salt bridges and main chain hydrogen bonds show an increase in the majority of thermophilic proteins in comparison to their mesophilic homologues. In addition, in thermophilic proteins hydrophobic residues are significantly more frequent, while polar residues are less. These findings indicate that thermostable proteins through evolution adopt several different strategies to withstand high temperature environments.