Objective: Cryptosporidium parvum is a protozoan parasite that is common case of diarrhea in both animals and humans worldwide. There is no effective specific chemotherapeutic intervention for cure. Objective of this study was comparative of anticryptosporidial effect of Monensin, Toltrazuril and the mix of them at 24 and 48 hours on oocysts of Cryptosporidium parvum in Hank’s balance salt solution (HBSS). Materials and Methods: The effects of various preparations of two anticoccidial drugs (Monensin and Toltrazuril) and the mix of them on oocysts of Cryptosporidium parvum at 24 and 48 hours in HBSS were studied. Oocysts of C. parvum were isolated from the fecal samples of calves and stored in HBSS in 4°C until use. Different concentrations of Monensin and Toltrazuril and the mix of them (0, 0.1, 0.5, 1, 10, 20, 60 and 100 [µgml] ^ (-1)) made by HBSS were exposed for 24 and 48 hours on the oocysts of C. parvum. The effects of the drugs on the purified C. parvum oocysts were evaluated by counting the complete oocysts with four sporozoites after 24 and 48 hours incubation at 37°C. Results: The results showed a significant decrease in the oocysts number related to the increase in the concentration and exposure time of the drugs. The mix of two drugs had the highest efficacy on the C. parvum oocysts than each of drugs alone at 24 and 48 hours (p<0.001). In addition, Monensin in contrast to Toltrazuril at the same concentration showed to be more effective on C. parvum oocysts at 24 and 48 hours (p<0.001). Conclusion: This study show that two drugs (Monensin and Toltrazuril) was effective on C. parvum oocysts and in addition, Monensin was more efective than Toltrazuril and the mix of them beacase of synergism effect was more effective than each of them alone. Thus can be using these drugs for cure of cryptosporidial infections.