Postoperative pain is a frequent complication of root canal treatment. It could worse patients’ quality of life (QoL) and it may be associated to several factors, including the shaping technique. The aim of the study was to compare the impact of WaveOne Gold (WOG) and WaveOne Classic (WOC) reciprocating instrumentation on postoperative QoL after single-visit primary root canal treatment. Healthy subjects with pulp necrosis on multirooted teeth were observed. Canal shaping was performed with WaveOne Gold Primary (n = 25) or WaveOne Classic Primary (n = 29) and canal filling was completed with a carrier-based technique. Mean and maximum scores for postoperative pain were assessed through a Visual Analogue Scale (VAS) and QoL indicators were evaluated with a self-assessment questionnaire based on a Likert scale. Postoperative pain curves were similar in both groups (mean pain p = 0.43; maximum pain p = 0.27) and quality of life indicators showed no significant differences (p > 0.05). There was a more favourable trend of QoL values in the WOG group, reaching statistical significance on day six posttreatment (p = 0.021). Within the limitations of the study, reciprocating instrumentation may have an impact on patients’ QoL, but the innovative geometrical and alloy properties of the WaveOne Gold seemed to induce a faster resolution of the postoperative symptoms.