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Background Miltefosine (MF) is the only oral drug available for treatment of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). Although the drug is effective and well tolerated in treatment of VL, the efficacy and safety of MF for longer treatment durations (>28 days) in PKDL remains unclear. This study provides an overview of the current knowledge about safety and efficacy of long treatment courses with MF in PKDL, as a strategy in the VL elimination in South Asia. Methodology/Principal findings Literature was searched systematically for articles investigating MF treatment in PKDL. A meta-analysis included eight studies (total 324 PKDL patients) to estimate the efficacy of MF in longer treatment regimens (range 6–16 weeks). We found a per-protocol (PP) initial cure rate of 95.2% (95%CI 89.6–100.8) and a PP definite cure rate of 90% (95%CI 81.6–96.3). Descriptive analysis showed that 20% of patients experienced adverse events, which mostly had an onset in the first week of treatment and were likely to get more severe after four weeks of treatment. Gastrointestinal (GI) side effects such as vomiting, nausea, diarrhoea, and abdominal pain were most common. Conclusions/Significance Longer treatment regimens with MF are effective in PKDL patients in India, however with the caveat that the efficacy has recently been observed to decline. GI side effects are frequent, although mostly mild or moderate. However, on the basis of limited data, we cannot conclude that longer MF treatment regimens are safe. Moreover, VL and PKDL pharmacovigilance studies indicate a risk for serious adverse events, questioning the safety of MF. The provision of safer treatment regimens for PKDL patients are therefore recommended. Until these regimens are identified, it should be considered to halt the use of MF monotherapy for PKDL in order to preserve the drug’s efficacy., Author summary In this study, we reviewed the available literature on the subject of safety and efficacy of the oral drug miltefosine in the treatment of post-kala-azar dermal leishmaniasis (PKDL). Literature was searched systematically in the PubMed database and eight articles, with a total of 324 PKDL patients, were included. A meta-analysis was performed to estimate the percentage of patients cured after longer (>4 weeks) miltefosine treatment. An estimated 90% of patients was found to be cured one year after treatment with miltefosine. In addition, descriptive analysis showed that nearly 20% of the PKDL patients suffered from side-effects. The majority of these side-effects, such as vomiting, nausea, diarrhea and abdominal pain, were mild and related to the gastro-intestinal tract. The findings of this study show that miltefosine is effective, although the efficacy has been observed to decline. The gastro-intestinal side effects were frequent but mostly mild. However, based on the limited data in this study we cannot conclude that longer treatment regimens with miltefosine are safe. In order to preserve the drug’s efficacy, we suggest it may be put under consideration to halt the use of miltefosine monotherapy for PKDL until alternative treatment regiments (e.g. short combination therapies including miltefosine) are identified.