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The purpose of this study was to report the clinical efficacy of decompression for 3 cases with large periapical lesions and to review technique details. Three cases with large periapical cystic lesions were treated with decompression after root canal treatment. A traditional decompression technique was used for the first case. After aspiration, mucogingival incision, irrigation, and incisional biopsy, a pediatric endotracheal tube was sutured in place and kept for 3 weeks for lesion debridement. An aspiration/irrigation technique was adopted for the second case. An 18-G needle with a syringe was used to aspirate the cystic lesion. Two needles were then inserted into the lesion; copious saline irrigation was delivered from 1 needle and until clear saline was expressed from the other. For the third case, decompression was accomplished with a surgical catheter that was subsequently replaced with a gutta-percha plug after 1 month. None of the 3 cases underwent complete enucleation and root-end surgery. Healed lesions or lesions in healing were observed after 1 to 2 years. Based on the presented cases and published case reports on decompression, a literature review was provided covering indications, technique details, modification, and prognosis of decompression in endodontics. For large periapical cystic lesions, conservative decompression may be used for certain cases before or in lieu of apical surgery. Decompression enables healing of large, persistent periapical lesions after root canal treatment.