To compare the incidence of surgical site infection-inflammation in dogs undergoing elective orthopedic surgery of the stifle after draping with a single-layer Kraton elastic seal patient drape or conventional double-layer drapes. Prospective clinical trial. A total of 789 dogs. Dogs were assigned to one of two groups: (1) conventional draping with 4-corner drapes and an overlying patient drape (n=390) or (2) a Kraton seal extremity patient drape without 4-corner drapes (n=399). All dogs were evaluated for surgical site infection-inflammation by 21 days and 6months postoperatively. The distribution of surgical procedures did not differ between draping techniques and included tibial tuberosity advancement (TTA, n=480), tibial plateau leveling osteotomy (TPLO, n=10), extracapsular lateral suture (ECLS, n=130), medial patellar luxation repair (MPL, n=63), lateral patellar luxation repair (LPL, n=1), ECLS/MPL (n=68), TTA/MPL (n=12), TTA with joint capsule biopsy (n=1), and stifle arthroscopy combined with TTA or TPLO (n=24). Duration of follow up was 180 days (range 3-180 days) for clinical examinations and 182 days (range 2-182 days) for phone communications. Infection-inflammation was documented in 9 dogs after double-layer draping and 11 dogs after single-layer draping at 21 days postoperatively and in 12 dogs after double-layer draping and 7 dogs after single-layer draping at 6 months postoperatively. No difference in postoperative infection-inflammation was detected between canine stifle surgeries draped with a single-layer Kraton extremity patient drape or double-layer drapes. The single-layer Kraton extremity patient drape is a viable alternative to conventional double-layer draping in canine stifle surgery.