He will be encouraged by the absence of the defending champion, home favourite Scott Piercy, who has switched from Reno to the lucrative World Golf Championships-Bridgestone Invitational in Akron, Ohio, after qualifying through his one-shot victory in the recent Canadian Open.
After 13 years as a stroke-play event, the Reno-Tahoe organisers have made the unusual switch to a modified Stableford system where points are scored for birdies and eagles.
It is designed to encourage aggressive play on the low-scoring Jack Nicklaus-designed course at the Montreux Golf Club, where the record is 61.
Harrington currently languishes at 28th in the European money list for the Ryder Cup with three tournaments to come before captain Jose Maria Olazabal's selection deadline.
But he will be encouraged by five consecutive top-20 finishes immediately before the Open, where he finished on a modest five over par in a tie for 39th.
His main opposition on the Reno course a mile above sea level could come from US trio John Rollins, JB Holmes and Chris Kirk, who tied for fourth in the Canadian Open, and the in-form South Korean Seung-Yul Noh.
"I obviously would have loved to defend in Reno, but this is a step in the right direction for my career," said Piercy, who, according to PGA Tour regulations, would not have been allowed to defend.