A treatment duration of 1 month past resolution of radiographic infiltrates, with a minimum of 90 days treatment, has been recommended for dogs with pulmonary blastomycosis.This retrospective study design had inherent limitations. A 2‐tailed Fisher's exact test was used to compare groups with regard to sex, survival at 2 weeks, representation for relapse, presence of individual factors comprising the disease severity score, and incidence of increases in ALT activities, with Medical records of 144 dogs with a diagnosis of blastomycosis were retrospectively reviewed. Of 66 dogs treated with fluconazole, 36 dogs met the inclusion criteria; 9 dogs died within 2 weeks of starting treatment, and 27 completed a full course of treatment. Infectious Diseases Society of AmericaUtility of diagnostic tests for and medical treatment of pulmonary blastomycosis in dogsGeneric substitution of itraconazole resulting in sub‐therapeutic levels and resistanceHepatotoxicity induced by antifungal drugs itraconazole and fluconazole in ratsAntigen and antibody testing for the diagnosis of blastomycosis in dogsPharmacokinetics and tissue penetration of fluconazole in humansClinical practice guidelines for the management of blastomycosisTreatment of blastomycosis with higher doses of fluconazole. The criteria for inclusion in the study were (1) a cytologic or histopathologic diagnosis of blastomycosis, or consistent clinical signs combined with a positive urine Blastomyces antigen test and response to treatment with antifungal drugsSignalment, history, clinical signs, and physical examination findings at the time of diagnosis were recorded for all dogs. Clinical remission was defined as resolution of all clinical signs, including absence of abnormalities on physical examination and ophthalmic examination (or remaining lesions considered inactive); chest or limb radiography (or interpreted as static over sequential radiographs taken 1 month apart); and imaging of any other affected sites. No statistically significant differences were found in age (The median disease‐severity score for dogs in both groups was 4, with a range of 2–8 for dogs treated with itraconazole and 1–7 for dogs treated with fluconazole (Dogs treated with itraconazole received a median dose of 5.5 mg/kg/d, ranging from 4.6 to 10.8 mg/kg/d. In all 9 cases, therapy was initially started using itraconazole and was then subsequently switched to fluconazole. The median age at the time of diagnosis was 5.0 years (0.8–11 years), with a median weight of 29.0 kg (6.2–49.0 kg). Dogs received a score of “1” if the clinical sign was present or if the body system was involved. The median age at the time of diagnosis was 5.5 years (range, 1.2–12.3 years), with a median weight of 29.0 kg (6.4–52.0 kg). It did not allow for dogs to have the same dosing and monitoring schedule. Six of 23 dogs (26%) in the itraconazole group that were evaluated had ALT activities that increased out of the reference range after starting therapy, compared with 3/18 dogs (17%) receiving fluconazole; this difference was not significant (Nine of the 144 dogs reviewed were censored from group analyses because of treatment with both itraconazole and fluconazole. A score of “0” was assigned if the clinical sign was not present or the body system was not involved. 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