BACKGROUND Fractures of the distal third of the humeral shaft remain a challenge today. Plate osteosynthesis is the most commonly used method of treatment. Current minimally invasive plate osteosynthesis (MIPO) techniques applied to the distal part of the humerus have shown a high risk of radial nerve injury, and they are unable to adequately fix distal-most fractures. Our hypothesis was that using a new MIPO approach, distal humeral shaft fractures can be safely fixed. The aim of this study was to develop this new anteromedial-distal MIPO approach. METHODS We conducted a laboratory descriptive study using 16 arms from adult human specimens. A new anteromedial-distal MIPO approach, starting distally through a small window in the pronator teres muscle, was developed. A premolded plate was introduced in the anterior side of the medial epicondylar area, through the anterior face of the humerus, up to the proximal part of the humeral shaft. Several anatomical parameters were measured on dissection to define the distances of the plate and screws to the neurovascular structures that could be at risk. RESULTS The radial nerve was not at risk because of its pathway through the posterior and lateral aspects of the arm. The mean distance from the most distal border of the medial epicondyle to the proximal border of the coronoid fossa was 3.36 cm (95% confidence interval [CI], 3.23 to 3.50 cm). At least 3 screws could be inserted in all specimens in this area and up to 5 when the fixation area was extended 2 cm proximally. The mean width of the medial epicondylar area was 2.19 cm (95% CI, 2.03 to 2.33 cm), space enough for the distal fixation of the plate. The ulnar nerve was at risk only from the tip of the most distal screw (mean distance of 2.50 mm; 95% CI, 1.60 to 3.40 mm) in specimens with a very narrow medial epicondylar area. CONCLUSIONS This approach provides adequate fixation for distal humeral shaft fractures, but proper clinical studies must be undertaken. CONCLUSIONS This new approach avoids the risk of radial nerve injury.