Cardiac resynchronization therapy (CRT) has a symptomatic and survival benefit for patients with heart failure (HF), but the percentage of nonresponders remains relatively high. The aims of this study were to assess the clinical significance of baseline tricuspid regurgitation (TR) or worsening TR after implantation of a CRT device on the response to therapy. This is a multicenter retrospective analysis of prospectively collected databases that includes 689 consecutive patients who underwent implantation of CRT. The patients were divided into groups according to baseline TR grade and according to worsening TR within 15 months after device implantation. Outcome was assessed by clinical and echocardiographic response within 15 months and by estimated survival for a median interquartile range follow-up time of 3.3 years (1.6, 4.6). TR worsening after CRT implantation was documented in 104 patients (15%). These patients had worse clinical and echocardiographic response to CRT, but worsening of TR was not a significant predictor of mortality (p = 0.17). According to baseline echocardiogram, 620 patients (90%) had some degree of TR before CRT implant. Baseline TR was an independent predictor of worse survival (p <0.001), although these patients had significantly better clinical and echocardiographic response compared with patients without TR. In conclusion, worsening of TR after CRT implantation is a predictor of worse clinical and echocardiographic response but was not significantly associated with increased mortality. Baseline TR is associated with reduced survival despite better clinical and echocardiographic response after CRT implantation.