Objective: To compare the efficacy and side effects of sublingual misoprostol and intravenous methylergometrine for active management of third stage of labor. Method: One hundred twenty low risk pregnant women at term with spontaneous onset of labor were included in the study. The women were randomized to receive either two tablets of misoprostol (200 μ g/tablet) sublingually or 1 ml of methylergometrine (200 μ g) intravenous injection, after the delivery of the anterior shoulder of the baby. The main outcome measures were: need for additional oxytocic drugs, blood loss ≥ 500 ml, change in hemoglobin levels and side effects. Results: Postpartum hemorrhage as defined by hemorrhage ≥ 500 ml occurred in 3.1% of the women in the sublingual misoprostol group but none of the women in the methylergometrine group (P > 0.05). There was a need for additional oxytocic drugs in 5.0% and 8.3% after methylergometrine and misoprostol, respectively (P > 0.05). The change in hemoglobin levels at 24 h postpartum were 0.8 and 0.7 mg% in methylergometrine and misoprostol group, respectively(P > 0.05). In the misoprostol group, 6.6% women developed fever ≥ 38° C and 21.6% had shivering while in methylergometrine group none experienced these side effects. However, the incidence of other side effects like nausea, vomiting, headache and giddiness were similar in both groups. Conclusion: Sublingual misoprostol appears to be as effective as intravenous methylergometrine in the prevention of postpartum hemorrhage. However, larger randomized studies are needed to advocate its routine use. Objective: To compare the efficacy and side effects of sublingual misoprostol and intravenous methylergometrine for active management of third stage of labor. Method: One hundred twenty low risk pregnant women at term with spontaneous onset of labor were included in the study. The women were randomized to receive either two tablets of misoprostol (200 μg / tablet) sublingually or 1 ml of methylergometrine (200 μg) intravenous injection, after the delivery of the anterior shoulder of the baby. The main outcome measures were: need for additional oxytocic drugs , blood loss ≥ 500 ml, change in hemoglobin levels and side effects. Results: Postpartum hemorrhage as defined by hemorrhage ≥ 500 ml occurred in 3.1% of the women in the sublingual misoprostol group but none of the women in the methylergometrine group (P> 0.05). There was a need for additional oxytocic drugs in 5.0% and 8.3% after methylergometrine and misoprostol, respectively (P> 0.05). The change in hemoglobin levels at 24 h postpartum were 0.8 and 0.7 mg% in methylergometrine and misoprostol groups, respectively (P> 0.05). In the misoprostol group, 6.6% women developed fever ≥ 38 ° C and 21.6% had shivering while in methylergometrine group none experienced experienced effects. However, the incidence of other side effects like nausea, vomiting, headache and giddiness were similar in both groups. Conclusion: Sublingual misoprostol appears to be as effective as intravenous methylergometrine in the prevention of postpartum hemorrhage. However, larger randomized studies are needed to advocate its routine use.