Chronic non-cancer pain (CNCP) is a major health problem. Patients are increasingly treated with chronic opioid therapy (COT). Several laboratory studies have demonstrated that long-term use of opioids does not generally impair driving related skills. But there is still a lack of studies investigating on-the-road driving performance in actual traffic. The present study assessed the impact of COT on road-tracking and car-following performance in CNCP patients. Twenty CNCP patients, long-term treated with stable doses of opioid analgesics, and 19 healthy controls conducted standardized on-the-road driving tests in normal traffic. Performance of controls with a blood alcohol concentration (BAC) of 0.5 g/L was used as a reference to define clinically relevant changes in driving performance. Standard Deviation of Lateral Position (SDLP), a measure of road-tracking control, was 2.57 cm greater in CNCP patients than in sober controls. This difference failed to reach statistical significance in a superiority test. Equivalence testing indicated that the 95% CI around the mean SDLP change was equivalent to the SDLP change seen in controls with a BAC of 0.5 g/L and did not include zero. When corrected for age differences between groups the 95% CI widened to include both the alcohol reference criterion and zero. No difference was found in car-following performance. Driving performance of CNCP patients did not significantly differ from that of controls due to large inter-individual variations. Hence in clinical practice determination of fitness to drive of CNCP patients who receive opioid treatments should be based on an individual assessment.