On November 8, 2011 about 1100 mountain standard time, the pilot of a Piper PA-31T Cheyenne II, N39EH, made a precautionary landing at Cheyenne Regional/Jerry Olson Field Airport (CYS), Cheyenne, Wyoming, after the airplane’s main cabin door separated from the airframe in-flight about 20 miles north of the airport. The airline transport pilot, two crew members and passenger were not injured and the airplane sustained substantial damage to the aft fuselage door frame assembly. The airplane was registered to La Stella of Wilmington, Delaware and operated by Travelaire Service, Inc, Pueblo, Colorado. The on-demand air medical flight was operated under the provisions of 14 Code of Federal Regulations Part 135. Visual meteorological conditions prevailed and an instrument flight rules flight plan was filed for the cross country flight. The flight originated from Cheyenne Regional/Jerry Olson Field Airport (CYS) about 1040 with a planned destination of Sheridan, Wyoming (SHR). The pilot reported that the airplane was climbing through 7,500 feet, for 12,500 feet, when he noted a pressurization issue and leveled the airplane at 8,500 feet. He consulted the checklist; however, was not able to rectify the situation and initiated a turn back to the departure airport. Soon thereafter, the airplane’s master caution horn sounded and the door unsafe light illuminated followed by a rush of air in the cockpit. The pilot returned to the departure airport and landed without further incident. The medical flight crew reported that about 20 minutes after takeoff, the main cabin door opened in-flight; the door subsequently separated from the aircraft. The main cabin door was later recovered and examined by a senior materials engineer at the National Transportation Safety Board’s materials laboratory, Washington DC. The examination revealed that the door hinge was fractured from the lower end of the door, and the hinge remained attached to the airplane. Rivets at the forward end of the hinge line were fractured, and the door outer skin was fractured in the hinge rivet line. Skin fractured around several of the rivets, and the saw-tooth pattern of fracture around the rivets was consistent with fracture propagation from forward to aft. Deformation was observed on the outer skin on the lower end of the door; the skin deformation was consistent with the door rotating downward and aft relative to the hinge attachment. The fracture surfaces were examined and all surfaces showed deformation and/or features on slant planes consistent with ductile overstress fracture. No evidence of preexisting cracks was observed. Internal panels were disassembled from the door to view the door structure and latching mechanism. All pushrods, latch pins and associated bellcrank were in place and intact. Wear was observed on the upper side of the forward pins at the middle and upper positions; however, the latching mechanism travel and extension of the pins was correct. No other anomalies were noted. A complete materials laboratory examination report is contained in the public docket for this accident.