The aim of this study was to compare the effectiveness and safety of intramuscular phloroglucinol and oral misoprostol for cervix pretreatment before diagnostic hysteroscopy. Several modalities for cervical priming and pain reduction have been adopted to reduce the complications related to cervical dilatation before hysteroscopy. Among them, the prostaglandin analog misoprostol is the most frequently used agent. Phloroglucinol, a spasmolytic, has also been showed to have an effect in inducing cervical dilatation but is rarely used before hysteroscopy. One hundred twenty outpatients undergoing anesthesia-free diagnostic hysteroscopy were randomly assigned to receive 80 mg intramuscular phloroglucinol and 400 mg oral misoprostol before diagnostic hysteroscopy. The main outcome measures were preoperative cervical width, visual analog scales (VAS) for pain, cervical passage time, and adverse reactions. Intramuscular phloroglucinol resulted in a significantly wider cervical width, lower VAS pain score, shorter cervical passage time, and a lower adverse effects rate compared with oral misoprostol. Intramuscular phloroglucinol is more effective and safer than oral misoprostol in inducing proper cervical priming and may be the optimal choice for cervical pretreatment before diagnostic hysteroscopy.