It is not recommended to mix carriers, especially on the same direction of a trip. For example, if you are traveling from Charlottesville to Los Angeles with a connection in Chicago. It is not a good idea to travel on American Airlines from Charlottesville to Chicago and Delta from Chicago to Los Angeles. The airlines do not always work well together so if you have a delay on one which causes you to miss the next flight the second airline may not be as likely to help since it was not their fault that you missed their flight. This could also require you to claim and re-check baggage in a connecting city, which could result in a missed connection.
Often flight itineraries will have an outbound flight on one airline and a return on another. This is less risky as long as you complete your travel. However, if you need to cancel your ticket, you will have two separate credits, therefore potentially have two separate change fees to reuse your credits. Whenever possible it is best to book your round trip ticket on the same airline.
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