Controversy still exists regarding the optimal method for post-operative skin closure in orthopedic surgery. In total knee replacement, closure with metal staples is faster but carries a higher surgical site infection (SSI) risk. Other studies have found differing results in foot and ankle and hip surgery. Very little evidence exists on this subject after spine surgery. The aim of this study was to determine whether closure of the skin incision in open posterior spine surgery carries a different rate of post-operative SSI when using nylon sutures compared with metal staples. Up to 2006, virtually all skin incisions at our spine surgery unit were closed with metal staples and from 2006 onward with nylon sutures. This was a retrospective historical control study comparing the incidence of SSIs in patients operated on before (n = 127; staples) and after (n = 143; sutures) the transition date. The staples group had an overall 11.8% combined deep and superficial infection rate whereas the nylon suture group had a 4.2% rate (p = 0.017). The two groups also differed in the type of antibiotic prophylaxis used, likelihood of incisional discharge, and the number of days the vacuum drains remained. In our departmental setting, closure of the skin incision with nylon sutures after open posterior spine surgery carried a significantly lower risk of post-operative SSI compared with metal staples. The generalizability of our findings is unclear, but they warrant further investigation.