Synchronous posterior retroperitoneoscopic bilateral adrenalectomy (PR-BilA) is a novel technique proposed for the definitive cure of hypercortisolism when a surgical approach is indicated. The aim of the present prospective cohort study was to compare the carbon dioxide (CO2) absorption in patients undergoing PR-BilA with those undergoing single posterior retroperitoneoscopic adrenalectomy (PRA). Twenty-nine patients undergoing PR-BilA or PRA were consecutively enrolled. Anaesthesia was standardised. In both groups, CO2 elimination (VCO2), CO2 dissolved in arterial blood (PaCO2), end-tidal CO2 (EtCO2), and volume per minute (VM) were measured at the following time points: after anaesthesia induction and before CO2 insufflation (T1), 5 min after CO2 insufflation (T2), at the time of maximum VCO2 (T3), and at desufflation (T4). VCO2 was continuously measured using a metabolic monitor. ANOVA for repeated measures was used for statistical analysis. With respect to VCO2, a significant group × time interaction was found (p = 0.03). Post hoc analysis revealed that VCO2 was significantly increased at T4 compared with T1 in both groups (p = 0.02 and p = 0.0001 in the PRA and PR-BilA groups, respectively). Regarding PaCO2, ANOVA analysis showed a significant group effect (p = 0.01), with higher values in the PR-BilA group. EtCO2 and VM did not differ between the two groups. We found that the CO2 absorption was increased in both groups at the end of surgery, in the presence of a higher trend in PaCO2 values during PR-BilA. Therefore, PR-BilA may be considered a safe surgical approach with respect to CO2 absorption, when a mild degree of hypercapnia may be accepted.