A project 16 years in the making, Parc Adula was lobbying for national park status, which would have made the 1,250km2 area only the country's second such park and the first for more than 100 years.
But on Sunday eight of the 17 communes in the cantons of Graubünden and Ticino affected by the park voted against the project, leaving backers sorely disappointed.
Several of the ‘no' votes were unexpected, said news agencies, since it was predicted that 13 of the communes would vote in favour, rather than the nine that actually did.
Particularly disappointing to supporters was the ‘no' from voters in Blenio, a commune in Ticino, of which 54km2 would have fallen within the park.
Under federal law, a national park must include at least 100km2 within the Alps. With Blenio's refusal, that cannot be achieved.
In a statement, the Swiss Parks Network acknowledged that the “combination of development and restrictions in the central zone of the park was obviously not welcomed with enthusiasm by the majority of the population of the communes in question”.
Environmental organization Pro Natura said the refusal was a “chance wasted”, but emphasized that the project had highlighted the desire for sustainable and ecological development in the region.
Switzerland was one of the first countries in Europe to create a national park, simply called the Swiss National Park, back in 1914.
However it now lags far behind other European countries in terms of numbers of parks, partly due to Switzerland's direct democracy system which means residents always have a say.
Last week Swiss media reported that many people in the communes affected by Parc Adula were against it gaining national park status because of the restrictions that would be placed on hunting, farming, tourism and other activity in the region.
The Swiss Parks Network awaits an analysis of the voting results to understand exactly why residents rejected the park's creation.
The analysis will have a “significant impact” on another national park project, Locarnese, located in Ticino, it said.
That project is due to go to the polls at the end of 2017.
The negative result for Parc Adula “shows fairly clearly what challenges are posed by the creation of a new national park in Switzerland”.