This study describes the anatomy of the posterior interosseous nerve and proposes how to protect it during the different approaches to the proximal radius. Based on the findings presented here, the choice of the approach and the pitfalls that might cause posterior interosseous nerve injury were defined. Three surgical approaches were used on 30 cadaveric upper limbs: modified Henry's anterior approach, Thompson's posterior approach, and a modified Gordon-Boyd's approach. Important anatomic structures were localized, marked, and shown on radiographs. Plates and screws were applied through the different approaches to determine the relationship of the hardware to the posterior interosseous nerve. Measurements were taken between the humeroradial joint, as a reference point, and different important anatomic structures. It was concluded that the anterior approach to the proximal radius is relatively safe and offers the possibility of proximal and distal extension. Caution should be taken while applying screws, however, to avoid posterior interosseous nerve injury. The radius is superficial posteriorly, and many surgeons favor Thompson's approach for exposure of the proximal radius; nonetheless, it carries the risk of posterior interosseous nerve injury with exposure of the most proximal portion of the radius. The modified Gordon-Boyd's approach offers the advantage of exposing both the radius and the ulna, but necessitates excessive muscle stripping.