Chasing a target of 290 off 50 overs, O'Brien, who came in a number three, hit 109 from 137 balls but did not get the support from his teammates as the Irish were eventually bowled out for 238 inside 46 overs.
O'Brien tried to keep Ireland's game alive, but after he became the eighth man out for 109, Ireland's chances of springing an upset were all but dashed.
Left-arm spinning allrounder Santner claimed four of the last five wickets, including that of centurion Niall O'Brien, after Ireland had threatened to run down New Zealand's 289-7.
He finished with 5-51 and was named player of the match.
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After their opening game in the series against Bangladesh was abandoned due to rain on Friday, Ireland were keen to register a win in the Malahide Cricket club.
The next tri-series fixture on Wednesday sees New Zealand take on Bangladesh, whose opener against Ireland was washed out.
After being asked to bat first, three New Zealand batsmen scored half-centuries, led by 79 off 63 balls from Neil Broom which added much-need impetus over the closing stages.
Porterfield won his second successive toss but it was New Zealand opener Luke Ronchi who got the innings off to a fast start with 37 from 26 balls, before he got a leading edge to a pull shot and was caught at point.
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The wicket-taker was Barry McCarthy, who can surprise batsmen with his pace, and as a result he has a habit of taking wickets in his first two overs.
Santner had earlier taken a fine catch off his own bowling to dismiss Andrew Balbirnie for 36 and end a productive third-wicket partnership with O'Brien after they had made 86 runs. Worker, in only his third global, was the more patient while Taylor scored at nearly a run-a-ball.
Peter Chase could not continue his good early season form, going for 74 runs and taking his only wicket in the last over.
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