A section of State Highway 2, at Karangahake, was closed for more than seven hours after a crash critically injured two people and seriously injured another.
Emergency services were called to the two-vehicle collision, between Paeroa and Waihi, about 3.15pm Thursday.
A St John spokesman said two ambulances and three helicopters were sent.
St John treated three patients who were airlifted to Waikato Hospital - two in a critical condition and one in a serious condition.
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A person with minor injuries was taken to Thames Hospital.
Police said in a statement at 10.45pm, the road had been cleared and reopened.
During the closure, diversions were in place at SH2 and SH26, SH2 and Orchard Rd, and at SH2 and Waitawheta Rd.
The Serious Crash Unit had been advised.