The objective of this study was to obtain an estimate of the pharmacokinetic parameters of moxidectin administered at a dosage of 1 mg/kg orally and topically to healthy adult giraffe (Giraffa camelopardalis). The maximum plasma concentration (C_MAX) of moxidectin after oral and topical administration was 69.2 ± 4.6 and 18.6 ± 16.1 ng/ml (P = 0.045), respectively. The areas under the plasma curve (AUC), a measure of total drug exposure, was 532.0 ± 232.3 and 209.1 ± 180.0 day*ng/ml (P = 0.308) for the oral and topical administrations, respectively. These data suggest moxidectin achieves higher peak plasma concentrations following oral administration compared with topical (transdermal) administration using the cattle pour-on formulation. Additionally, the percent coefficient of variation, a measure of variability, was smaller for the oral formulation (C_MAX %CV = 7%; AUC %CV = 44%) compared with the topical formulation (C_MAX %CV = 86%; AUC %CV = 86%). The smaller variability suggests that oral administration of moxidectin produces more predictable and less variable drug absorption than topical administration in giraffe and is the preferred route of administration.