Introduction:High relapse rate of nonmuscle invasive bladder cancer (NMIBC) is a major challenge. Overexpression of microRNA-21 (miR-21) which targets phosphatase and tensin homolog (PTEN), a gene associated with malignancy, has been reported in the bladder tumor tissue compared to normal mucosa by us and others. We have tested whether miR-21 levels in bladder mucosa could predict tumor recurrence.Methods:In a prospective cohort setting, tumor tissues and normal bladder mucosa (NBM) were taken from BC patients during transurethral resection of bladder tumor. Age- and ethnicity-matched NBM from benign prostate hyperplasia patients was taken as controls. The expression of miR-21 was analyzed using quantitative reverse transcription polymerase chain reaction. Patients were followed for 4 years for tumor reoccurrence. Postoperative recurrence were recorded and calculated by Kaplan–Meier curve.Results:In 31 patients, miR-21 was up-regulated (>4-fold, P = 0.003), and PTEN levels were significantly lower (<7-folds, P = 0.001) in tumor tissue relative to NBM. Moreover, the fold change in miR-21 levels was significantly higher (>3-folds, P = 0.03) in patients showing recurrence compared to those in which tumor did not recur. Further, Kaplan–Meier analysis shows overexpression of miR-21 corresponds to less time to recurrence with higher cumulative hazard.Conclusion:We found overexpression of miR-21 in tumor tissue and its association with recurrence, time to recurrence and invasiveness in BC. Quantification of miR-21 along with other pathological parameters could be more objective molecular approach to predict recurrence in NMIBC.