Surgical site infections (SSIs) are associated with significant consequences in orthopaedic surgery, where their presence can lead to ultimate revision of the implant. Furthermore, infections and impaired wound healing can prolong length of hospital stay following orthopaedic surgery, which can place additional financial burdens on healthcare systems. The current analysis was conducted to determine whether the use of the PICO single-use negative pressure wound therapy (sNPWT) system after orthopaedic surgery reduced the incidence of SSIs and length of hospital stay compared with using conventional dressings. A systematic literature review (SLR) was performed using the PubMed, Embase and Cochrane Library databases. English-language studies comparing PICO sNPWT to conventional dressings published from 2011 to August 2018 with ≥10 patients in each treatment arm were included. Reference lists of included studies were searched for further relevant studies. Meta-analyses were performed using a fixed effect (I² < 50%) or random effects model (I² ≥ 50%). The SLR identified 6,197 studies, of which 5 relevant studies (607 patients) were included. The odds of an SSI were reduced by 57% (odds ratio [OR]: 0.43; 95% confidence interval [CI]: 0.21–0.86; p = 0.02) and there was consistency between studies (I² = 0%). Three studies reported on length of hospital stay. The mean difference between patient groups indicated that PICO sNPWT was associated with a 1-day reduction in hospital stay (mean difference [MD]: −0.99; 95% CI: −1.32 to −0.65; p < 0.00001) and there was again consistency between studies (I² = 0%). These results suggest that the use of PICO sNPWT system after closed surgical incisions can reduce the incidence of SSIs and shorten the duration of hospital stay when used in orthopaedic patient populations.