
Adagio Medical Holdings, Inc. This prospectus supplement updates and supplements the information contained in the prospectus dated February 7, 2025 (as maybe supplemented or amended from time to time, the “Prospectus”), which forms part of our registration statement on Form S-1 (FileNo. 333-284266) with the information contained in our Current Report on Form 8-K that was filed with the Securities and ExchangeCommission on December 11, 2025 (the “Current Report”). Accordingly, we have attached the Current Report to this prospectussupplement. The Prospectus and this prospectus supplement relate to the offer, sale or other disposition from time to time of up to 67,963,695shares of our common stock, $0.0001 par value per share (the “Common Stock”), by the selling stockholders named in the Prospectusor their permitted transferees (collectively, the “selling stockholders”), consisting of (i) up to 7,951,913 shares of Common Stock(excluding the shares of Common Stock underlying the PIPE Warrants (as defined below)) (the “PIPE Shares”) and 110,000 shares ofCommon Stock (the “Registration Delay Shares”) issued pursuant to the terms of the Convert Waivers (as defined below), (ii) up to670,000 shares of Common Stock issuable upon exercise of pre-funded warrants to purchase shares (the “Pre-Funded WarrantShares”) of Common Stock, with an exercise price of $0.01 per share (the “Pre-Funded Warrants”), (iii) up to 7,528,727 shares ofCommon Stock (the “PIPE Warrant Shares”) issuable upon exercise of warrants to purchase shares of Common Stock, with anexercise price of $10.00 per share (the “PIPE Warrants”), in each of cases (i) through (iii), issued pursuant to those certain amendedand restated subscription agreements, dated July 31, 2024 (the “Subscription Agreements”), by and among us, ARYA SciencesAcquisition Corp IV, a Cayman Islands exempted company (“ARYA”), and certain selling stockholders named therein (the “PIPEInvestors”) at an effective price of approximately $7.10 per PIPE Share and/or Pre-Funded Warrant, (iv) up to 46,717,980 shares ofCommon Stock (excluding the shares of Common Stock underlying the Convert Warrants (as defined below)) (the “Convertible NoteShares”) issuable upon the conversion of those certain 13% senior secured convertible notes, with a conversion price of $10.00 pershare, subject to adjustment as provided in the Convertible Security Subscription Agreement (as defined below), (the “ConvertNotes”), (v) up to 900,000 shares of Common Stock (the “Convert Warrant Shares”) issuable upon exercise of warrants to purchaseshares of Common Stock, with an exercise price of $24.00 per share, subject to adjustment as provided in such warrants (the “ConvertWarrants” and, together with the PIPE Warrants, the “Warrants”), in each of cases (iv) and (v), issued pursuant to that certain securitiespurchase agreement, dated February 13, 2024, by and among us and certain investors named therein (the “Convert Investors”), and anyassignment thereunder (the “Convertible Security Subscription Agreement”), and that certain note purchase agreement, dated February13, 2024, by and among us, Adagio Medical, Inc., a Delaware corporation, and Perceptive Life Sciences Master Fund, Ltd, a CaymanIslands exempted company (the “2024 Bridge Financing Note Subscription Agreement”), (vi) up to 2,354,100 shares issued to ARYASciences Holdings IV, a Cayman Islands exempted company (the “Sponsor”), consisting of 499,000 shares of Common Stock thatwere initially issued to Sponsor in a private placement as Class A ordinary shares of ARYA at a price of $10.00 per share andexchanged for shares of Common Stock at Closing (as defined below) (the “Sponsor Class A Conversion Shares”), 1,500,000 shares ofCommon Stock that were initially issued to Sponsor as Class B ordinary shares of ARYA at an effective price of approximately $0.007per share and exchanged for shares of Common Stock at Closing (the “Sponsor Class B Conversion Shares”), and 355,100 shares ofCommon Stock that were originally issued to Sponsor as Class A ordinary shares of ARYA upon the conversion of certain convertiblepromissory notes issued by ARYA at an effective price of $10.00 per share and exchanged for shares of Common Stock at Closing (the“Sponsor Working Capital Shares”), (vii) up to 582,475 shares of Common Stock, consisting of 492,475 shares of Common Stockissued to certain of our affiliates as consideration in connection with the Business Combination (as defined below) at an equityconsideration value of approximately $9.23 per share and 30,000 shares of Common Stock issued to each of Michael Henderson, ToddWider and Leslie Trigg (collectively, the “Independent ARYA Directors”), which were originally issued as Class B ordinary shares ofARYA, valued at approximately $0.007 per share, (viii) up to 1,147,500 shares of Common Stock issuable to the Sponsor that aresubject to share trigger price vesting and will vest if, prior to the tenth anniversary of the Closing, the p




