Driven back by a succession of storms, it was not until April 17, 1625, that the fleet was able to leave the Channel and put out to sea.

The voyage was a rapid one and on May 23, Hendrikszoon sailed into the bay in battle order, only to see the Spanish flag waving over San Salvador and the mighty fleet of Admiral Toledo drawn up under the protection of its batteries.
Hendrikszoon sailed slowly past the Spaniards, who did not stir, and perceiving that it would be madness to attack a superior force in such a position he reluctantly gave orders to withdraw.

On the homeward journey by the West Indies a number of rich prizes were made, but sickness made great ravages among the crews, and counted Hendrikszoon himself among its victims.
The events of the following year seem to show that with audacity he might have at least inflicted heavy losses on the enemy.

For in 1626 the directors, ignorant of his failure, sent out a reinforcement of nine ships and five yachts under the command of the redoubtable Piet Hein.
Hein sailed on May 21 for the West Indies, where he learnt that Hendrikszoon was dead and that the remnant of his expedition had returned after a fruitless voyage of misadventure.

Hein however was not the man to turn back.