Grapevine trunk diseases (GTD) are caused by several fungal species and are major limiting factors to vineyard productivity and profitability in all viticulture areas. This study is aimed at addressing the gap in the knowledge with regards to measuring the long-term benefits of post-pruning fungicide application on trunk diseases incidence and crop yield in grape production systems. It also calculated the net economic benefit of implementing such practice over the vineyard lifespan. We selected a newly planted commercial table grape vineyard in the California desert and divided it in two blocks. In one block, the registered fungicide thiophanate-methyl was mechanically applied on pruning wounds for six consecutive years, while the other half remained untreated. Our results showed a significant lower GTD incidence and vine replants in treated blocks combined with a significant increase of total and marketable fruit. Potential annual economic benefits of applying fungicide on pruning wounds appear to be in the range of $8500–$12,500 per hectare annually in a 50–75% disease control scenario.