In the 2021 season Letterman Lanigan Racing again expanded to three cars, with Graham Rahal and Takuma Sato driving two full-time entries while several drivers would drive a third car on a part-time basis. Santino Ferrucci took the seat in the third entry, #45 baked by HyVee, a chain of supermarkets in the Midwestern and Southern United States, in five races. He scored four top-10 finishes, including 6th in the Indy 500 and 6th in the first race at Detroit, and ended the season in 24th position with 146 points.
|Santino Ferrucci||45||Rahal Letterman Lanigan Racing|
|Dallara DW12 (IR18)||Honda||HyVee|