A patient's health in an opioid maintenance program is potentially endangered due to concurrent consumption of drugs. Therefore, the German Medical Association requests evidence of compliant substitute intake while type and frequency of drug screening is chosen by the physician. This study comparatively assessed the feasibility and potential advantage of oral fluid drug testing versus urine screening in day-to-day practice.Urine and oral fluid-samples of a randomly chosen third of a total of 361 patients, treated in four different practices in a major German city, were tested. The detection rates were compared bivariate and the illicit substance intake of subgroups were analysed. Additionally, patients' and employees' satisfaction with the test procedures were assessed.A total of 117 paired urine and oral fluid samples were considered for this study. A dual sample collection was not obtainable with 29 patients due to insufficient sample volume or refusal. Other than methadone or buprenorphine, 155 substances were found in urine samples, whereas only 82 other substances were detected in oral fluids. Significant differences existed within substance groups with THC being positive in 50 (42.7%) urine samples and only three (2.6%) positive oral fluid samples (p < 0.0001) and with benzodiazepines with 41 (35%) positive urine and 28 (23.9%) positive oral fluid samples (p < 0.0001), respectively. In total 75.2% of the urine samples were positive for concurrent drug consumption. Employees and patients did not prefer one test type over the other.The confirmation of concurrent drug intake in maintenance setting is generally possible by the use of oral fluid, but inferior to urine screening.