The effect of the AirSeal
®
insufflation system on hemodynamic parameters, especially end-tidal carbon dioxide (EtCO
2
), 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 EtCO
2
, peripheral capillary oxygen saturation (SpO
2
), and arterial systolic blood pressure (ABP), were collected and analyzed. EtCO
2
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 EtCO
2
≥ 3 mmHg in addition to decreases in SpO
2
≥ 3% and ABP ≥ 10 mmHg simultaneously, which suggest possible carbon dioxide (CO
2
) embolism. The median EtCO
2
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 EtCO
2
of proctectomy was significantly higher than that of gastrectomy during the whole and pneumoperitoneum periods (
P
< 0.05). In contrast, the EtCO
2
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 CO
2
embolism. Positive responses occurred during venous exposure or bleeding in all nine cases. Although the EtCO
2
of hepatectomy was comparable to that of the other surgeries using the AirSeal
®
, laparoscopic hepatectomy showed a tendency of CO
2
embolism. Thus, a secure and careful surgical approach is mandatory for laparoscopic hepatectomy using the AirSeal
®
insufflation system.