A new protocol for the selected omission of transsyndesmotic fixation in Weber class C ankle fractures was prospectively evaluated in 21 consecutive patients. As proposed in a previous cadaveric study (J. Bone Joint Surg., 71A:1548-1555, 1989), the protocol suggested that transsyndesmotic fixation was not required if (1) rigid bimalleolar fracture fixation was achieved or (2) lateral without medial fixation was obtained (i.e., with accompanying deltoid tears) if the fibular fracture was within 4.5 cm of the joint. According to this protocol, only 3 of 21 patients (14%) required transsyndesmotic fixation. Ten of the patients who did not receive transsyndesmotic fixation underwent pronation-external rotation stress radiographs in a fashion analogous to the previous cadaveric study. At 1- to 3-year follow-up, no stress (N = 10) or static view (N = 18) widening of the mortise or syndesmosis was seen in any patient, which supports (with the above guidelines) a limited, rather than routine, use of supplemental transsyndesmotic fixation. Clinical results from this prospective study seem to substantiate previously proposed biomechanical guidelines for the selected omission of transsyndesmotic fixation. Given these guidelines, transsyndesmotic fixation was unnecessary in many cases and the need can be determined before surgery by assessing the integrity of the deltoid ligament and level of the fibular fracture.