Objectives: This study aimed to systematically review the pain and flare-up effects of calcium hydroxide (CH) as intracanal medication (ICM) in non-vital mature teeth. Materials and Methods: Electronic-databases searching for published and grey literature and manual searching were conducted. Only randomized clinical trials (RCTs) were included comparing CH to other ICMs in non-vital mature teeth. The risk of bias was assessed using the RoB 2.0 Cochrane tool. The main outcomes were pain and flare-up.Qualitative and quantitative analysis, wherever applicable, was performed. The certainty of evidence (CoE) was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Sixteen articles were included in 6 comparisons at different time points for different outcomes. CH reduced pain risk than no ICM within the 1–14-days interval (p < 0.05) and than triple-antibiotic paste within the first day (p < 0.05) and was similar to corticosteroid/ antibiotics combination (p > 0.05). Chlorhexidine (CHX) or CH/CHX, however, reduced pain levels than CH alone (p < 0.05). CH showed higher flare-up risk than CHX (p < 0.05). CoE, however, ranged from very low to moderate. Conclusion Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another.Therefore, further well-designed, larger RCTs are required.

Objectives: This study aimed to systematically review the pain and flare-up effects of calcium hydroxide (CH) as intracanal medication (ICM) in non-vital mature teeth. Materials and Methods: Electronic-databases searching for published and grey literature and manual searching were conducted. Only randomized clinical trials (RCTs) were included comparing CH to other ICMs in non-vital mature teeth. The risk of bias was assessed using the RoB 2.0 Cochrane tool. The main outcomes were pain and flare-up.Qualitative and quantitative analysis, wherever applicable, was performed. The certainty of evidence (CoE) was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Sixteen articles were included in 6 comparisons at different time points for different outcomes. CH reduced pain risk than no ICM within the 1–14-days interval (p < 0.05) and than triple-antibiotic paste within the first day (p < 0.05) and was similar to corticosteroid/ antibiotics combination (p > 0.05). Chlorhexidine (CHX) or CH/CHX, however, reduced pain levels than CH alone (p < 0.05). CH showed higher flare-up risk than CHX (p < 0.05). CoE, however, ranged from very low to moderate. Conclusion Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another.Therefore, further well-designed, larger RCTs are required.