Sam Bennett was the width of a bicycle tyre away from winning his second consecutive stage at the Vuelta, however, the Carrick-on-Suir native had to settle for second place.
Nicolas Roche remains in the red leader's jersey after finishing in the bunch to record the same time as the stage winner.
Fabio Jakobsen, riding for the Deceuninck - Quick-Step team, secured the stage win, beating Bennett by the narrowest of margins at the finish in El Puig.
The Deceuninck-QuickStep rider edged out Bennett by a matter of millimetres in the flat finale to the 175 km ride along Spain's east coast from Cullera to El Puig to earn his first ever victory at a Grand Tour.
The stage, which contained only one classified climb and had a 20km flat finish, was one of the more straightforward routes of this year's Vuelta and was always going to favour the sprinters.
Bennett, who picked up a fourth Grand Tour stage win the previous day - his first at the Vuelta - looked to be on course for a stunning repeat victory but his decision to take a right turn rather than left at a roundabout as the final kilometre approached saw him lose valuable time.
Bennett recovered superbly in the last stretch of the stage but narrowly failed to unseat Jakobsen.
Bennett's second place finish earned 20 sprint bonus points and as a result the Bora-Hansgrohe rider now leads the category and will race in the green jersey in stage five on Wednesday.
Compatriot Roche holds a two-second lead in the general classification over second-placed Nairo Quintana while Rigoberto Uran is third, still eight seconds behind Roche despite being involved in a minor crash on Tuesday.
The Vuelta lost another high-profile name earlier in the day when Dutchman Steven Kruijswijk of Jumbo-Visma withdrew from the race with a sore knee which had become aggravated since being involved in a crash in the opening team time trial.
Wednesday's stage five is a 170km hilly ride from L'Eliana to Alto de Javalembre containing three classified climbs and is the first of eight summit finishes at this year's race.