OBJECTIVES: Prenatal distribution of misoprostol has been advocated as a strategy to increase access to uterotonics during the third stage of labor to prevent Post Partum Hemorrhage (PPH).  The objective of this study was to project the potential cost-effectiveness of this strategy in Uganda from both governmental (payer) and societal perspectives.  METHODS: To compare prenatal misoprostol distribution to the status quo (no misoprostol distribution), we developed a decision model that tracked the delivery pathways, outcomes and cost of a pregnant woman from the prenatal period to onset of labor, delivery without complications or delivery with PPH, and successful treatment or death.  Model parameters were derived from the Uganda Demographic and Health Survey and the published literature, as well as expert opinion.  We computed expected probabilities of PPH and death due to PPH, Disability Adjusted Life Years (DALYs) and costs.  In the incremental analysis, we calculated changes in expected probabilities of PPH and death due to PPH, Disability Adjusted Life Years (DALYs) and changes in costs.  We conducted univariate and probabilistic sensitivity analyses to examine robustness of our results.  RESULTS: In the base case analysis, the expected probabilities of PPH and death due to PPH were lower with prenatal misoprostol distribution (14.0% versus 16.3% and 1.4% versus 1.7% respectively).  Mean DALYs were lower with prenatal misoprostol distribution (0.408 versus 0.511).  Mean costs were lower with prenatal misoprostol distribution both from the governmental ($17.42 versus $18.27) and societal ($30.02 versus $31.55) perspectives.  In the incremental analysis, prenatal misoprostol distribution was a dominant strategy i.e. it was both less costly and more effective.  This result was robust to univariate and probabilistic sensitivity analysis.  CONCLUSIONS: Prenatal distribution of misoprostol is potentially cost-effective in Uganda.  It would potentially save lives and money and should be considered for national-level scale up for prevention of PPH.