INTRODUCTION: Fab antivenom (FabAV) halts progression of tissue injury and improves recovery in copperhead snakebite. It is unknown if F(ab')2AV does as well. The objective of this study was to compare control of tissue injury in copperhead snakebite patients treated with F(ab')2AV versus FabAV. METHODS: We performed a post hoc analysis of copperhead envenomated patients in a clinical trial comparing F(ab')2AV to FabAV. The outcomes for this analysis are the number of repeat doses required to obtain initial control, the number of patients requiring unscheduled doses during maintenance, and the time from antivenom administration to initial control. RESULTS: Twenty-one (13 F(ab')2AV, 8 FabAV) were copperhead patients. Median age was 46 years with a male predominance. Baseline severity was similar. One (8%) F(ab')2AV and 2(25%) FabAV patients required repeat initial dosing, difference = 17%, (95%CI -18, 57%). One (8%) F(ab')2AV and 1(13%) FabAV patients required additional doses after maintenance, difference = 5%, (95%CI -27, 45%). Median time to initial control was 2.7 range (2.0, 9.3) hours and 3.5 range (2.0, 7.4) for F(ab')2AV and FabAV respectively, difference -0.8 h (95% CI -2.6, 0.9). CONCLUSIONS: This exploratory analysis suggests that the available measures of the control of venom-induced tissue injury are similar between antivenom subgroups.