The pilot was initiating takeoff following completion of an annual inspection, which included replacing and repairing components of the right engine’s No. 1 cylinder, likely due to detonation that occurred during the flight before the accident flight. During the takeoff on the accident flight, witnesses noted significant smoke trailing the right engine at rotation. The witnesses noted that, as the airplane continued over the runway, the right engine lost power and the right propeller feathered. The landing gear retracted and, at the departure end of the runway, white/blue or white smoke was noted trailing the left engine, followed by a perceived loss of power from that engine. The airplane continued off-airport, encountered an aerodynamic stall, and impacted a tractor-trailer travelling on a nearby highway, resulting in a postimpact fire.Postaccident examination of the airframe revealed no evidence of preimpact failure or malfunction of the flight controls or flaps, and there was no evidence of an in-flight left engine fire. Examination of the engines revealed early signs of detonation on the No. 1 piston of the right engine. In addition, the No. 3 cylinder fuel injector nozzle of the left engine was not installed in the cylinder but remained attached to the fuel injector line throughout the flight. Given these findings, it is likely that both engines sustained a partial loss of engine power during takeoff.The witness reports of seeing smoke trailing the left engine when at the departure end of the runway were likely the result of the No. 3 cylinder fuel injector nozzle that was not installed on its respective cylinder. Based on blade impact angles and performance estimates from the propeller manufacturer, it is likely that the left engine exhibited about a 15% power reduction from full rated power during the takeoff. The reduction of left engine power and corresponding rpm would likely have been evident to the pilot from the moment of full power application until Page 2 of 13 ERA22FA126about 60 knots, at which point the airflow over the left propeller would have been sufficient for the propeller to operate at full rated rpm. The witness report of the right engine’s power loss and the feathering of the right propeller was likely the pilot’s response to the start of detonation in the No. 1 cylinder. Causes for detonation include improper ignition timing, high inlet air temperature, engine overheating, oil in the combustion chamber, carbon build-up in the combustion chamber, an issue with the fuel octane, or a lean fuel to air mixture.Although the position of the right mixture control at the start of the takeoff could not be determined from the available evidence, it is unlikely that the pilot would have leaned the fuel to air ratio, especially since it was the first takeoff after repairs due to detonation damage following a flight for which he was the pilot. In addition, operating the engines with the fuel to air ratio leaned during the accident takeoff would have been contrary to the takeoff procedure specified in the Pilot’s Operating Handbook and FAA-approved airplane flight manual.Aside from signs of detonation, the No. 1 cylinder and piston, spark plugs, fuel injector nozzle and line, manifold valve, and engine-driven fuel pump of the right engine were eliminated as having any evidence of preimpact failure or malfunction. Impact and/or heat damage, along with impact-separated components of the ignition system, including both magnetos and ignition harness, baffling, cowling, air induction, and fuel metering systems, as well as there being no remaining fuel due to the postimpact fire, precluded determination of preimpact failure or malfunction for these components.Although the root cause of detonation could not be determined from the available evidence, had maintenance facility personnel thoroughly investigated the fuel metering, ignition, and air induction systems and reviewed data from the engine monitor from the previous flight in which the No. 1 cylinder of the right engine exhibited detonation, it is likely that they could have identified and addressed any mechanical reason for the detonation.While moderate atherosclerosis was detected in one segment of the pilot’s left anterior descending coronary artery, there was no evidence to suggest an acute cardiac event occurred; from medical records, he was in good cardiovascular health. Although a disqualifying stimulant used to treat attention deficit hyperactivity disorder (ADHD) was detected during postaccident toxicological testing, the circumstances of this accident do not suggest inattention or fatigue. Thus, the pilot’s cardiovascular medical condition, the effects of his use of methylphenidate, and his ADHD were likely not factors in this accident.