Background: Androgen deprivation therapy (ADT) plays a pivotal role in management of prostate cancer (PC), with prolonged ADT favored over short-term use in the definitive treatment of high risk PC with radiation. Objectives: To compare cardiorespiratory fitness (CRF) and cardiovascular (CV) mortality among patients with PC with and without ADT exposure, and to explore how duration of ADT exposure influences CRF and CV mortality risk. Methods: This is a retrospective study of patients referred for exercise treadmill testing (ETT) after a diagnosis of PC. PC risk classification was based on Gleason score (GS) at diagnosis: high risk GS ≥ 8, intermediate risk GS= 7, and low risk GS ≤ 6. CRF was categorized according to metabolic equivalents (METs): METs ≥ 8 defined as good CRF and METs < 8 as reduced CRF. ADT exposure was grouped as short-term (≤ 6 months) versus prolonged (> 6 months). Results: 616 patients underwent an ETT a median of 4.8 years (interquartile range: 2.0-7.9) after diagnosis of PC. 150 patients (24.3%) received ADT prior to ETT; 51 with short-term versus 99 with prolonged exposure. 524 (85.1%) patients had ≥ 2 CV risk factors, and 28 CV deaths occurred over 4.2 (interquartile range: 2.3-7.1) years following the ETT. Reduced CRF was more frequent among ADT-exposed versus ADT-naive patients (48.7 versus 32.6%, p< 0.001). Prolonged ADT was associated with reduced CRF (odds ratio (OR): 2.71; 95% confidence interval (CI): 1.31-5.61; p=0.007) and increased CV mortality (hazard ratio (HR): 3.87; 95% CI: 1.16-12.96; p=0.03) in adjusted analyses. In contrast, short-term ADT exposure was not independently associated with either reduced CRF (OR 1.71; 95% CI: 1.00-2.94); p=0.05) or CV mortality (HR: 1.60; 95% CI: 0.51-5.01; p=0.42). Conclusions: Among patients with PC and high baseline CV risk, > 6 months ADT exposure but not less was associated with reduced CRF and increased CV mortality. Reduced CRF may in part mediate increased CV mortality risk. Exercise interventions concurrent with prolonged ADT warrants investigation to potentially offset risk.