According to FENZ, one person suffered critical injuries, one serious injuries and one moderate injuries.
St John Ambulance said two patients in a serious condition were transported to Hawke's Bay Hospital.
Police said a stretch of the beachfront highway was closed after the three-vehicle crash, but was cleared and reopened by midnight.
The crash occurred about 1.7km south of SH51's intersection with Ellison St at the southern entrance to Napier's Marine Parade.
A detour was available via Te Awa Ave, past Napier Boys' High School and the Maraenui Golf Club.
Two fire trucks and three ambulances attended the scene.
The narrow two-lane highway, with wire-rope barriers on either side, has been the subject of calls for the speed limit to be lowered from 100kmh to 80kmh, in keeping with its role as a tourist and holidaymakers' route.
It is also a busy route from Havelock North and Clive to Napier and a major route between Napier and Hastings.
The same stretch of SH51 was closed for several hours four weeks ago, after what was the fifth fatal crash on the highway in just over two and a half years.
There have been other serious crashes on the 3km stretch, and emergency services extricated a patient from a vehicle after another crash near the Ellison St intersection last Thursday.