This study was performed to evaluate the efficacy of a recent oral antiprotozoal agent, Miltefosine, in the treatment of canine leishmaniasis due to Leishmania infantum. A multicentre field trial was conducted in 20 veterinary practices in France, Spain and Italy. Eighty-two dogs were included in the study with a canine leishmaniasis, based on clinical examination and confirmed by positive serology, myelogram and/or PCR analysis. Dogs were treated with a Miltefosine-based oral solution at 2 mg/kg body weight once a day for 28 days. They were clinically observed 6 times: V1 (pre-inclusion and sampling), V2-Day 0 (inclusion and start of treatment), V3-Day 14, V4-Day 28 (end of treatment and sampling), V5-Day 42 and V6-Day 56. Efficacy was assessed by the percent reduction of the clinical score, veterinarians' opinion, the time course of the clinical score, the percent parasitological cure, the albumin/globulin ratio and serology. On average, Miltefosine treatment reduced the clinical score by 61.2 ± 44.9% in 8 weeks. In 82.7% of cases, veterinary investigators considered treatment with miltefosine retrospectively as or more effective than conventional antileishmanial treatment (Meglumine antimoniate - Allopurinol association). The clinical score decreased significantly over the 2-month follow-up period (p<0.0001). Clinical response was markedly visible during the 4 weeks of treatment and continued to improve in the 4 weeks after completion of treatment. 51.5% of dogs were parasitologically cured on Day 56 according to the myelogram. In 24.1% of cases with an albumin/globulin ratio < 0.7 at V1, the ratio became > 0.7 at V6. A decrease of at least one dilution in IFAT titres was recorded in 37.2% of dogs over the 8-week follow-up period. Miltefosine given orally at 2 mg/kg once a day for 28 days proved to be an effective and convenient new alternative to treat canine leishmaniasis.