The effect of the AirSeal® insufflation system on hemodynamic parameters, especially end-tidal carbon dioxide (EtCO2), during laparoscopic abdominal surgery remains unclear. This retrospective single-center study included 333 consecutive patients who underwent laparoscopic hepatectomy (n = 43), gastrectomy (n = 69), colectomy (n = 137), or proctectomy (n = 84) using the AirSeal®. Patient demographics and intraoperative hemodynamic parameters, such as EtCO2, peripheral capillary oxygen saturation (SpO2), and arterial systolic blood pressure (ABP), were collected and analyzed. EtCO2 was evaluated during the entire operative period (whole period) as well as the pneumoperitoneum period until specimen removal (pneumoperitoneum period). We defined "positive respiratory and circulatory responses" (positive responses) as a decrease in EtCO2 ≥ 3 mmHg in addition to decreases in SpO2 ≥ 3% and ABP ≥ 10 mmHg simultaneously, which suggest possible carbon dioxide (CO2) embolism. The median EtCO2 values of hepatectomy, gastrectomy, colectomy, and proctectomy in the whole period/pneumoperitoneum period were 37.3/37.4, 37.1/37.3, 37.4/37.9, and 38.2/38.4 mmHg, respectively. The EtCO2 of proctectomy was significantly higher than that of gastrectomy during the whole and pneumoperitoneum periods (P < 0.05). In contrast, the EtCO2 of hepatectomy was comparable to that of the other three surgeries in the whole and pneumoperitoneum periods. Meanwhile, nine (2.7%; eight hepatectomies and one proctectomy) patients showed positive responses, and one who underwent a partial hepatectomy developed a clinically manifested CO2 embolism. Positive responses occurred during venous exposure or bleeding in all nine cases. Although the EtCO2 of hepatectomy was comparable to that of the other surgeries using the AirSeal®, laparoscopic hepatectomy showed a tendency of CO2 embolism. Thus, a secure and careful surgical approach is mandatory for laparoscopic hepatectomy using the AirSeal® insufflation system.