Objectives To investigate the post-treatment apical periodontitis (AP) in endodontically treated teeth through a multivariate approach and to analyze the relative importance of quality and type of coronal restoration as predictors of periapical disease. Materials and Methods The present study sample was drawn within two-year period from the 1072 consecutive patients older than 18 years, first time attending the Dental Clinic of the Clinical Hospital Centre, Rijeka, Croatia. A total of 1350 endodontically treated teeth was included in clinical and radiological survey. For each tooth the periapical status, root filling quality, intracanal post, separated file presence, marginal bone loss, quality and type of coronal restoration were recorded. Statistical analysis Chi-square tests were used to analyze the variations in the periapical status regarding the tooth type, quality of root canal filling, post and separated file presence, marginal bone loss, as well as coronal restoration type and quality. Multivariate logistic regression (backward model) was used to assess the effect of explanatory variables on periapical status. The outcome variable was set as the presence versus absence of AP in the tooth. Results The proportion of periapical disease was significantly increased in teeth with inadequate quality of the root canal filling (χ2=314.30 ; p < 0.001) and coronal restoration (χ2=41.37 ; p < 0.001). No difference in the periapical status was detected regarding the presence of separated file, marginal bone loss or type of coronal restoration. Multivariate logistic regression analysis demonstrated that the length and density of the root canal filling are most significant variables associated with the AP presence (p<0.001). Variables intracanal post, separated file, marginal bone loss, and coronal restoration type and quality were not significantly associated with AP. Conclusion The results did not indicate any significant association between type or quality of coronal restoration with post-treatment AP. Conversely, it revealed that relative importance of root canal filling surpasses the other analyzed variables, making the length and density of root canal filing most important predictors for post-treatment periapical disease.