Background:Novel combinations of ivermectin (IVM) and fluazuron (FLU) are presented as an alternative for the control of ticks in cattle. Applying a combination of drugs with the aim to affect different stages of the parasite’s life cycle is established as a potential measure to achieve the control of ticks in cattle.Aim:To determine the therapeutic equivalence between two novel formulations of IVM 1% combined with FLU 12.5% tested on bovines naturally infested with Rhipicephalus (Boophilus) microplus.Methods:Forty adult beef cattle were randomized into four groups (n = 10): IVM [1% (0.2 mg/kg)], combinations groups A and B [IVM 1% (0.2 mg/kg) + FLU 12.5% (2.5 mg/kg), each], and control [untreated]). On days 14, 27, and 49 after administration, the presence of ticks was ranked as null, low, medium, and high; a cumulative link model was adjusted to evaluate treatment response.Results:Although all groups had some animals with the presence of ticks until day 27, on day 14 IVM [odds ratios (OR) 0.013, CI95%: 0.001–0.014, p < 0.01], A (OR 0.01, CI95%: 0.00–0.07, p < 0.01) and B (OR 0.01, CI95%: 0.00–0.148, p < 0.01) groups were different when compared to the control group, unlike on day 27 where only groups A (OR 0.02, CI95%: 0.00–0.17, p < 0.01) and B (OR 0.06, CI95%: 0.00–0.46, p < 0.01) remained different from the control group. On day 49 post-administration, IVM and B did not differ from the control group, with 0.95 probability (CI95% 0.92–1.02) of high parasite burden. At day 49 post-administration, group A was the only group free of ticks (OR 0.01, CI95%: 0.00–0.13, p < 0.01).Conclusions:Pharmacotechnical differences in combined formulations should be considered in therapeutic equivalence studies.