Boeing's Model 307 Stratoliner is often considered a sister airplane to the B-17. This was especially true and appropriate after the War, when war-weary C-75s were refurbished using a good deal of B-17G components. The original model was built using B-17C components except for the fuselage and some instrumentation. Lessons learned from flying the 307 were incorporated into later models of the B-17,

The Stratoliner was the first pressurized-cabin commercial airliner. Basically a prewar design, it seems to have been displaced in the market by the larger, faster Lockheed Constellation, resulting in a small number of Stratoliners being built overall.

Commercially, the planes were operated by Pan American and TWA. The TWA planes were drafted as C-75s during the war, while the PanAm planes continued in service to Latin America.