This study evaluated the accuracy of pulse oximetry, capnography, and oscillometric blood pressure during general anesthesia in giraffes (Giraffa camelopardalis). Thirty-two giraffes anesthetized for physiologic experiments were instrumented with a pulse oximeter transmittance probe positioned on the tongue and a capnograph sampling line placed at the oral end of the endotracheal tube. A human size 10 blood pressure cuff was placed around the base of the tail, and an indwelling arterial catheter in the auricular artery continuously measured blood pressure. Giraffes were intermittently ventilated using a Hudson demand valve throughout the procedures. Arterial blood for blood gas analysis was collected at multiple time points. Relationships between oxygen saturation as determined by pulse oximetry and arterial oxygen saturation, between arterial carbon dioxide partial pressure and end-tidal carbon dioxide, and between oscillometric pressure and invasive arterial blood pressure were assessed, and the accuracy of pulse oximetry, capnography, and oscillometric blood pressure monitoring evaluated using Bland-Altman analysis. All three noninvasive methods provided relatively poor estimates of the reference values. Receiver operating characteristic curve fitting was used to determine cut-off values for hypoxia, hypocapnia, hypercapnia, and hypotension for dichotomous decision-making. Applying these cut-off values, there was reasonable sensitivity for detection of hypocapnia, hypercapnia, and hypotension, but not for hypoxemia. Noninvasive anesthetic monitoring should be interpreted with caution in giraffes and, ideally, invasive monitoring should be employed.