Background: Patient discomfort secondary to an indwelling urethral catheter in the post operative period can be very distressing. These symptoms resemble the overactive bladder (OAB) syndrome. Muscarinic receptor blockers have been successful in the management of OAB. However, information on the use of these drugs in the management of the postoperative catheter-related bladder discomfort (CRBD) in sub-Saharan Africa is still relatively sparse. Objective: To assess the efficacy of preoperative oral tolterodine in the management of CRBD in surgical patients in the immediate postoperative period. Methods: This was a double-blind placebo-controlled study consisting of 56 patients in each arm who underwent general anesthesia. Each patient was given oral tolterodine or placebo 1 hour before the induction of anesthesia. The patient was later assessed at the recovery room at intervals after recovery from anesthesia. The presence of CRBD was noted and graded. Results: The overall incidence of CRBD in both the tolterodine group and the control were 85.7% and 91.1%, respectively. Overall, tolterodine prophylaxis (TP) was associated with an absolute risk reduction (ARR) of 5.4%, relative risk reduction (RRR) of 5.8%, and a number needed to treat (NNT) of 19. The incidence of moderate-to-severe CRBD in the tolterodine and control groups were 10.7% and 78%, respectively, with an ARR of 74.5% with TP. Conclusion: TP does not significantly reduce the incidence of CRBD in the immediate postoperative period but appears to be efficient in the reduction of the severity of postoperative CRBD.