Aims: (i) To carry out meta-analyses to quantify the influence of the clinical factors on the efficacy of primary root canal treatment and (ii) to identify the best treatment protocol based on the current evidence.

Methodology: The evidence for the effect of each clinical factor on the success rate (SR) of primary root canal treatment was gathered in three different ways: (i) intuitive synthesis of reported findings from individual studies; (ii) weighted pooled SR by each factor under investigation was estimated using random-effect meta-analysis; (iii) weighted effect of the factor under investigation on SR were estimated and expressed as odds ratio for the dichotomous outcomes (success or failure) using fixed- and random-effects meta-analysis. Statistical heterogeneity amongst the studies was assessed by Cochran's (Q) test. Potential sources of statistical heterogeneity were investigated by exploring clinical heterogeneity using meta-regression models which included study characteristics in the regression models.

Results: Out of the clinical factors investigated, pre-operative pulpal and periapical status were most frequently investigated, whilst the intra-operative factors were poorly studied in the 63 studies. Four factors were found to have a significant effect on the primary root canal treatment outcome, although the data heterogeneity was substantial, some of which could be explained by some of the study characteristics.

Conclusions: Four conditions (pre-operative absence of periapical radiolucency, root filling with no voids, root filling extending to 2 mm within the radiographic apex and satisfactory coronal restoration) were found to improve the outcome of primary root canal treatment significantly. Root canal treatment should therefore aim at achieving and maintaining access to apical anatomy during chemo-mechanical debridement, obturating the canal with densely compacted material to the apical terminus without extrusion into the apical tissues and preventing re-infection with a good quality coronal restoration.