Urine cytology and cystoscopy are routinely employed during follow-up of patients after trimodal therapy (TMT) for muscle-invasive bladder cancer (MIBC). The significance of positive or equivocal cytology without visible disease recurrence on cystoscopy during follow-up is unknown, and studies informing outcomes in this scenario are lacking. This study aims to investigate the temporal trends of positive/equivocal cytology in the absence of visible disease recurrence and the association with bladder cancer recurrence and survival outcomes. One hundred and twenty-nine patients with available post-TMT cytology data and negative cystoscopy from a single academic institution between 2002 and 2017 with a median follow-up of 3.4 (range 0.1-14.2) years were analyzed. Cytology results, first post-TMT cytology positive/equivocal (CP) and negative (CN), were evaluated for association with disease recurrence and survival. Kaplan. Meier and competing risks methods were used to assess time-to-negative cytology in CP patients with ≥2 interval post-TMT cytology results (n = 33), time-to-recurrence, and disease-specific mortality (DSM) stratified by first post-TMT cytology result. At first follow-up (6-8 weeks post-TMT completion), CP was observed in 41 (32%) and CN in 88 (68%) of patients. With further follow-up of CP patients with ≥2 interval post-TMT cytology results, the probability of developing negative cytology was 57% (95% CI 42, 77) at 6 months post-TMT, and the median time-to-negative cytology was 3.2 months (95% CI 2.99, 5.80). The median time-to-recurrence was reduced in CP patients compared to CN (24.3 vs. 78.1 months, p = 0.1), corresponding with an apparent increase in the cumulative incidence of recurrence rate at 3 years in the CP vs. CN group (62% vs. 42%, p = 0.1). No significant difference was observed in the 3-year DSM rates. On univariable analysis, the hazards of recurrence and DSM for patients with CP were 1.5 (95% CI 0.9, 2.5, p = 0.1) and 2.1 (95% CI 0.9, 4.7, p = 0.07) respectively. This is the first study to investigate the significance of a positive/equivocal cytology without visible disease following TMT for MIBC. Positive cytology is common and does not preclude subsequent negative cytology supporting a watchful waiting approach rather than proceeding immediately to biopsy. However, cytology that remains positive at subsequent follow-up may be associated with adverse recurrence and survival outcomes.