BACKGROUND: Several publications have measured the difficulty of third molar removal, trying to establish the main risk factors, however several important preoperative and intraoperative variables are overlooked. MATERIAL AND METHODS: A prospective cohort study comprising a total of 130 consecutive lower third molar extractions was performed. The outcome variables used to measure the difficulty of the extraction were operation time and a 100mm visual analogue scale filled by the surgeon at the end of the surgical procedure. The predictors were divided into 4 different groups (demographic, anatomic, radiographic and operative variables). A descriptive, bivariate and multivariate analysis of the data was performed. RESULTS: Patients' weight, the presence of bulbous roots, the need to perform crown and root sectioning of the lower third molar and Pell and Gregory 123 classification significantly influenced both outcome variables (p< 0.05). CONCLUSIONS: Certain anatomical, radiological and operative variables appear to be important factors in the assessment of surgical difficulty in the extraction of lower third molars.