The purpose of this study was to compare clinical, radiographic, and histopathologic effects of Nd:YAG laser pulpotomy to formocresol pulpotomy on human primary teeth. Patients with at least two vital primary molar teeth that required pulpotomy, because of pulpal exposure to caries, were selected for this study. After hemorrhage control, complete hemostasis into the canal orifice was achieved by exposure to Nd:YAG laser (1064 nm) and an He-Ne laser (the aiming beam of the Nd:YAG laser) in noncontact mode at 2 W, 20 Hz, 100 mJ, or was achieved by applying 1:5 dilution of formocresol. Forty-two teeth in two groups were to be followed up clinically and radiographic at 1, 3, 6, 9, and 12 months. Eighteen teeth planned for serial extractions were selected for histopathologic study. The teeth were extracted at 7 and 60 days. The teeth in the laser group had a clinical success rate of 85.71% and a radiographic success rate 71.42% at 12 months. The teeth in the formocresol group had a clinical and radiographic success rate of 90.47% at 12 months. There were no statistically significant differences between laser and formocresol group with regard to both clinical and radiographic success rates. There was a statistically significant difference between 7- and 60-day laser groups with regard to inflammatory cell response criteria. Dentin bridge was absent in all samples. No stained bacteria were observed in any of these samples. In conclusion, Nd:YAG laser may be considered as an alternative to formocresol for pulpotomies in primary teeth.