Aim To compare the accuracy of film and digital periapical radiography (PR) in detecting apical periodontitis (AP) using histopathological findings as a reference standard. Methodology Jaw sections containing 67 teeth (86 roots) were collected from nine fresh, unclaimed bodies that were due for cremation. Imaging was carried out to detect AP lesions using film and digital PR with a centred view (FP and DP groups); film and digital PR combining central with 10˚ mesially and distally angled (parallax) views (FPS and DPS groups). All specimens underwent histopathological examination to confirm the diagnosis of AP. Sensitivity, specificity and predictive values of PR were analysed using rater mean (n = 5). Receiver operating characteristics (ROC) analysis was carried out. Results Sensitivity was 0.16, 0.37, 0.27 and 0.38 for FP, FPS, DP and DPS, respectively. Both FP and FPS had specificity and positive predictive values of 1.0, whilst DP and DPS had specificity and positive predictive values of 0.99. Negative predictive value was 0.36, 0.43, 0.39 and 0.44 for FP, FPS, DP and DPS, respectively. Area under the curve (AUC) for the various imaging methods was 0.562 (FP), 0.629 (DP), 0.685 (FPS), 0.6880 (DPS). Conclusions The diagnostic accuracy of single digital periapical radiography was significantly better than single film periapical radiography. The inclusion of two additional horizontal (parallax) angulated periapical radiograph images (mesial and distal horizontal angulations) significantly improved detection of apical periodontitis.