Context: Postoperative hyperthermia, which may lead to cognitive decline, is a common complication of cardiovascular surgery with cardiopulmonary bypass (CPB). Aims: The aim of this study was to examine the effectiveness of perioperative intravenous acetaminophen on body temperature in adult patients after cardiovascular surgery with CPB. Settings and Design: This was a single-center retrospective study focusing on adult patients who underwent elective cardiovascular surgery with CPB at a university hospital in Japan. Subjects and Methods: Patients were divided into two groups based on whether they received acetaminophen perioperatively. In the acetaminophen group, 15 mg/kg intravenous acetaminophen solution was infused at 30 min after discontinuation of CPB and every 6 h after intensive care unit (ICU) admission. Statistical Analysis Used: The primary outcome was the maximum axillary temperature within 12 h after ICU admission. The effects of acetaminophen on postoperative body temperature were estimated by the standardization and inverse probability weighting using propensity scores. Results: A total of 201 patients were included in the final analysis (acetaminophen group, n = 101; non-acetaminophen group, n = 100). The maximum axillary temperature within 12 h after ICU admission was 37.20 ± 0.54°C in the acetaminophen group and 37.78 ± 0.59°C in the non-acetaminophen group. Acetaminophen lowered the standardized mean of primary endpoint (−0.54°C, 95% confidence interval, −0.69 to −0.38) compared to non-acetaminophen. Conclusions: Perioperative intravenous acetaminophen inhibited body temperature elevation after cardiovascular surgery with CPB, compared with the non-acetaminophen group.