Leptocybe invasa Fisher & La Salle is an important pest of Eucalyptus plantations in South Africa (SA) as it causes significant reduction in growth or mortality. A trial was implemented in 2012 in Zululand (KwaZulu-Natal) to determine the effect of regeneration method (coppice vs replant) on the susceptibility of a Eucalyptus grandis x E. camaldulensis clone (GC clone) to L. invasa. The trial consisted of three treatments that were replicated four times and laid out in a randomised complete block design. Treatments included: (1) coppiced GC clone, (2) re-planted GC clone and (3) a planted E. grandis x E. urophylla hybrid clone (GU clone) that was tolerant to L. invasa. The severity of L. invasa infection and tree performance was assessed annually, up to five years. Planted E. grandis x E. urophylla resulted in significantly improved tree growth (p < 0.001) when compared to planted and coppiced E. grandis x E. camaldulensis. In addition, the severity of L. invasa infection was low for E. grandis x E. urophylla over the five year period. Final assessments at five years indicated that, although tree growth measurements (diameter at breast height, height, volume and basal area) of coppiced E. grandis x E. camaldulensis was lower than of the planted material, the difference was not significant. Severity of L. invasa for both coppice and replanted E. grandis x E. camaldulensis was higher in years one to three. At year five, severity ratings of coppiced E. grandis x E. camaldulensis was not significantly different from that of the planted material. Results of invariable tree growth and L. invasa severity at five years indicate that coppice regeneration does not increase E. grandis x E. camaldulensis susceptibility to infection by L. invasa. Additional field studies are needed to evaluate a wide range of eucalypt species for their relative susceptibility to L. invasa as well as other major pests and diseases.