Driving has been regarded as an activity of daily living that is important in maintaining a person's independence in the community, access to employment, and social activities. Many patients, however, using opioid medications on a regular basis ( Chronic Opioid Analgesic Therapy: COAT) to ameliorate their intractable pain have been restricted from driving out of concern that skills would be impaired and driving safety compromised by these medications. Yet there are no driving studies which have explored the effects of using opioid analgesics for an extended period of time. This pilot study was designed to determine the effects of medically prescribed, stable opioid use on the driving abilities of patients with persistent, nonmalignant pain. Sixteen patients with chronic nonmalignant pain on COAT, who met criteria for participation in the study, underwent a comprehensive off-road driving evaluation using measures which have been shown to be sensitive in predicting on-road driving performance. The evaluation consisted of a pre-driver evaluation (PDE), a simulator evaluation (SDE), and behavioral observation during simulator performance. Patients in the COAT group were compared to a historical control group of 327 cerebrally compromised patients (CComp) who had undergone the same evaluation and then passed an on-road, behind-the-wheel evaluation (BTW Pass; n = 162) or failed (BTW Fail; n = 165). Results revealed that COAT patients generally outperformed the CComp patients as a group by equaling or exceeding PDE and SDE scores of the BTW Fail patients as well as the BTW Pass patients on all measures that differentiated the groups. Notably, COAT patients had a relatively poorer performance than CComp patients on specific neuropsychometric tests in the PDE; however, the differences were not statistically significant and did not imply a systematic pattern of scores that reflected domain-specific deficits. Behaviorally, COAT patients were generally superior to CComp patients, also; however, COAT patients had greater difficulty in following instructions and as well as a tendency toward impulsivity, like the BTW fail group. While there was general support for the notion that COAT did not significantly impair the perception, cognition, coordination, and behavior measured in off-road tests that have been regarded as requisite for on-road driving, methodological problems may limit the generalizability of results and recommendations are made for research beyond a pilot study.