Objective To assess the role of oral pentosan polysulphate (PPS) in the reduction of bacille Calmette-Guerin (BCG)-related local side effects in patients with high grade Ta/T1 non-muscle-invasive bladder cancer (NMIBC). Patients and Methods A total of 32 symptomatic patients receiving BCG instillation were randomized into three groups: group A received placebo (vitamin B complex tablet) thrice daily; group B received PPS 100 mg thrice daily; and group C received PPS 100 mg once daily and placebo (vitamin B complex tablet) twice daily for 6 weeks. A visual analogue scale (VAS) score for bladder pain, Overactive Bladder-Validated 8 Question Screener (OAB-V8) scores and dysuria were evaluated in the three groups before and during each weekly visit for BCG instillation. Results The mean +/- SD post-treatment VAS scores were significantly lower in groups B (4.4 +/- 1.2) and C (5.8 +/- 0.8) than in group A (8 +/- 0.4). In addition, the post-treatment VAS score was significantly lower in group B than in group C (P<0.01). The mean post-treatment OAB-V8 score was significantly lower only in group B (decreased from 15.5 to 9.7). Dysuria decreased in groups B and C but persisted in group A. Conclusion The present study shows that oral PPS (100 mg) thrice daily is effective in relieving BCG-related local side effects.