Objectives Current literature is in disagreement regarding female sex as a risk factor for pain after surgery. We hypothesized, that sex differences exist but that they are influenced by certain factors. Here, we investigated the influence of sex for different clinically relevant postoperative pain ( POP) outcome parameters and evaluated the role of assumed confounders for sex differences. Methods From 1372 screened patients undergoing orthopedic surgery at the university hospital of Muenster between March 2010 and June 2011, 890 patients were included. The validated International Pain Outcomes questionnaire was used to assess the role of sex for several aspects of POP including pain severity, physical and emotional functional interference as well as the patient's perceptions of the care they received on the first day after surgery. Assessed confounders were age, preoperative chronic pain, anesthetic technique employed and surgical procedure. All statistical analyses were performed with SPSS Statistics Software 22. Results Linear regression analysis demonstrated that sex was a statistically significant risk factor for "worst pain since surgery". Additionally, significant sex differences in "time spent in severe pain", "feeling anxious due to pain", "feeling helpless due to pain" and "opioid consumption since surgery" could be identified. An univariate general linear model showed that "age" and "preoperative pain" were significant confounders for sex differences. Further descriptive subgroup analysis revealed consistent sex differences for several POP outcome variables especially in patients older than 50 years or patients with preoperative chronic pain. However, sex differences disappeared in younger patients and in patients without preoperative pain. Discussion Our data confirmed that sex differences exist in pain intensity and frequency, pain interference with feelings and opioid consumption during the first 24 hours postoperatively. However, sex differences were significantly influenced by the factors "age" and "preoperative pain". These findings may in part explain why clinical studies get different results related to sex differences and renders specific awareness in older women and female patients with preoperative chronic pain.