In stress-positive, unstable supination-external rotation type 4 (SER IV) ankle fractures, implant selection for syndesmotic fixation is a debated topic. Among the available syndesmotic fixation methods, the metallic screw and the suture button have been routinely compared in the literature. In addition to strength of fixation and ability to anatomically restore the syndesmosis, costs associated with implant use have recently been called into question. This study aimed to examine the cost-effectiveness of the suture button and determine whether suture button fixation is more cost-effective than two 3.5-mm syndesmotic screws not removed on a routine postoperative basis. Economic and decision analysis; Level of evidence, 2. Studies with the highest evidence levels in the available literature were used to estimate the hardware removal and failure rates for syndesmotic screws and suture button fixation. Costs were determined by examining the average costs for patients who underwent surgery for unstable SER IV ankle fractures at a single level-1 trauma institution. A decision analysis model that allowed comparison of the 2 fixation methods was developed. Using a 20% screw hardware removal rate and a 4% suture button hardware removal rate, the total cost for 2 syndesmotic screws was US$20,836 and the total effectiveness was 5.846. This yielded a total cost of $3564 per quality-adjusted life-year (QALY) over an 8-year time period. The total cost for suture button fixation was $19,354 and the total effectiveness was 5.904, resulting in a total cost of $3294 per QALY over the same time period. A sensitivity analysis was then conducted to assess suture button fixation costs as well as screw and suture button hardware removal rates. Other possible treatment scenarios were also examined, including 1 screw and 2 suture buttons for operative fixation of the syndesmosis. To become more cost-effective, the screw hardware removal rate would have to be reduced to less than 10%. Furthermore, fixation with a single suture button continued to be the dominant treatment strategy compared with 2 suture buttons, 1 screw, and 2 screws for syndesmotic fixation. This cost-effectiveness analysis suggests that for unstable SER IV ankle fractures, suture button fixation is more cost-effective than syndesmotic screws not removed on a routine basis. Suture button fixation was a dominant treatment strategy, because patients spent on average $1482 less and had a higher quality of life by 0.058 QALYs compared with patients who received fixation with 2 syndesmotic screws. Assuming that functional outcomes and failure rates were equivalent, screw fixation only became more cost-effective when the screw hardware removal rate was reduced to less than 10% or when the suture button cost exceeded $2000. In addition, fixation with a single suture button device proved more cost-effective than fixation with either 1 or 2 syndesmotic screws.