Abstract Objectives To compare the efficacy and tolerability of propiverine and oxybutynin in patients with neurogenic detrusor overactivity. Methods Patients were eligible, if at least 18 years of age and suffering from neurogenic detrusor overactivity. Eligibility also required a maximum cystometric capacity less than 300 ml. After a one-week run-in period, propiverine 15 mg t.i.d. or oxybutynin 5 mg t.i.d. were administered for 21 days. As primary efficacy outcomes urodynamic parameters were assessed. As tolerability outcome the percentage of patients with newly manifesting anticholinergic adverse events was taken. Results 131 patients were recruited at 20 study centers. The maximum cystometric capacity (ml) was increased significantly in the propiverine group from 198 (±110) to 309 (±166), and in the oxybutynin group from 164 (±64) to 298 (±125). Similarly, maximum detrusor pressure during the filling phase (cm H 2O) was lowered significantly in the propiverine group from 56.8 (±36.2) to 37.8 (±31.6), and in the oxybutynin group from 68.6 (±34.5) to 43.1 (±29.2). No significant differences resulted between treatment groups. Anticholinergic adverse events were reported less frequently in the propiverine compared to the oxybutynin group (63.0% versus 77.8%). Dryness of the mouth, the most frequent adverse event, was reported significantly less (47.1% versus 67.2%; p = 0.02) in the propiverine compared to the oxybutynin group. Conclusion Propiverine and oxybutynin are equally effective in increasing bladder capacity and lowering bladder pressure in patients with neurogenic detrusor overactivity. The trend for better tolerability of propiverine compared to oxybutynin achieved significance for dryness of the mouth.