Introduction: This study sought to determine the effects of residual root canal bacteria and treatment factors on endodontic treatment outcomes up to 6 years post-operatively using traditional radiography (PA radiographs) and limited cone beam computed tomography (CBCT). Methods: Root canal samples were obtained from 50 patients with pulp necrosis and a periapical lesion, following two-visit treatment using contemporary chemomechanical preparation techniques. PCR, with broad range 16S rDNA bacterial primers, was performed followed by cloning and sequencing on pre-obturation specimens. Periapical and CBCT radiographs were taken at 10 months to 6 years post-treatment. Images were scored by two blinded, calibrated endodontists using the conventional periapical index (PAI) and a CBCT index. Statistical analysis was performed using bivariate and multivariate regression analysis for treatment factors. Kaplan-Meier survival analysis and Pearson's regression analysis was used for year-over-year changes. Results: 41 patients were included in the final data analysis. Recall decreased from 98% at 10-17 months to 51% at 33+ months. The percentage of patients healed at 10-17 months, 18-32 months and 33+ months and overall was 65%, 63%, and 66% respectively. Factors influencing outcomes were presence of bacteria at time of obturation (56% when present, 81% absent), primary versus persistent disease (71% vs. 39%), tooth type (85% anterior,23% molar), obturation to the radiographic apex (100% to the apex, 56% not to the apex), and larger master apical file sizes (73%MAF>45 vs. 36% MAF<45).. Short-term outcomes had a strong positive relationship with final outcome (Pearson's, r2=0.56, p=<0.01). Conclusions: Bacterial DNA presence at the time of obturation adversely affects short-term and intermediate-term endodontic treatment outcomes, but this effect is not found in the long-term. Various patient factors such as tooth type and treatment factors such as master apical file size influence outcomes. Short-term treatment outcomes are good predictors of long-term outcomes.