Cost
The Lexus ES 350 won't tax your gas budget substantially more than the Lexus IS 250 will.
Producing an accurate fuel economy evaluation is so tricky that some think not even the federal government can do it, but it looks as though both the Lexus ES 350 and the Lexus ES 350 perform about comparably when it comes to gas mileage.
With respect to MSRP, the Lexus ES 350 doesn't cost much less than the IS 250.
Utility
Neither the Lexus IS 250 nor the Lexus ES 350 has a marked advantage regarding seating capacity.
Convenience
The Lexus IS 250's fuel tank will need to be replenished a little more often than the unit in the Lexus ES 350.
Comfort
While the front cabin in the Lexus ES 350 offers a bit more head room than the Lexus IS 250, there frankly isn't much of a difference.
The ES 350 offers more head- and leg-room to your passengers than the Lexus IS 250 does.
Dimensions
The Lexus IS 250's tank is roughly the same size as the Lexus ES 350's, though the ES 350's is a little bigger.
The Lexus IS 250 and the Lexus ES 350 compete for the same parking spaces.
Performance
In terms of horsepower, the Lexus ES 350 packs quite a punch and will knock the Lexus IS 250 down a few rungs. On the flip side, keep in mind that high horsepower engines often command higher insurance premiums.
Handling
With its tighter turning circle, the Lexus IS 250 is definitely more maneuverable than the Lexus ES 350, something to consider if you do a lot of city driving; however, note that a vehicle with a tight turning circle may feel a bit twitchy on the highway.
Drivetrain
The ES 350's engine is considerably more massive than the Lexus IS 250's. Bear in mind that bigger engines may use more gas than smaller ones.
The Lexus ES 350 packs quite a wallop compared to the Lexus IS 250 in terms of torque, which is the force that lets you accelerate quickly.
Torque equals pickup, and the Lexus ES 350 will have picked up and gone by the time the Lexus IS 250 finally gets moving.
Warranty
The Lexus ES 350 and the Lexus IS 250 have the same basic after-sale protection.