Originally Posted by TravelwhileyouEat

I would book with the Airline directly especially if the savings is only 10-20% of what the ticket is worth, ex. on the airline site it's $200 and the OTA it's $160. They usually get to price the lower fare by selling a more restrictive fare sub-bucket which means that changes or cancellations would mean extravagant fees. Also, some OTAs have 'admin fees' on top of cancellation or change fees that the airline imposes.

Another thing to note with the comment of Aliquot about delays. If you are booking a connecting flight, example MSY - ATL - LHR, some OTAs will book you on 2 separate tickets (sometimes on 2 separate airlines) in order to get you the cheaper fare. This will mean that your 2 segment is not protected.

Example: You bought your ticket on OTA.com and the first flight from MSY - ATL is on AA and your next flight from ATL to LHR is on British Airways (BA) with a 4 hour connection. This may seem like enough time, but what happens if your AA flight is delayed and arrives 4 hours late? BA will state that it's not their problem since they only hold your booking as ATL-LHR and you missed your flight. AA will also state that it got you to ATL and you're only booked with them up to ATL. You will need to contact the OTA to fix this but most likely you'll get the runaround and it will just ruin your trip and cost you extra.

On the other hand, I have booked connecting flights on OTAs but that's because it was discounted by as much as 50% from what was available on the airline's website. This was all on 1 ticket on 1 airline so I was protected by delays same as if I was booking with the airline directly.