Abstract Although an expanding array of effective treatments has resulted in recent improvement in survival of patients with mantle cell lymphoma (MCL), outcomes remain heterogeneous, and identification of prognostic factors remains a priority. We assessed the prognostic impact of time to progression of disease (POD) after first-line therapy among 455 patients with relapsed MCL. Patients were categorized by duration of first remission as PRF/POD6, defined as progressive disease during induction or POD within 6 months of diagnosis (n = 65; 14%); POD6-24, defined as POD between 6 and 24 months after diagnosis (n = 153; 34%); and POD>24, defined as POD >24 months after diagnosis (n = 237; 53%). The median overall survival from POD (OS2) was 1.3 years (95% confidence interval [CI], 0.9-2.4) for patients with PRF/POD6, 3 years (95% CI, 2-6.8) for those with POD6-24, and 8 years (95% CI, 6.2-NR) for those with POD>24. Median OS2 was inferior in patients with early POD (defined as PRF/POD6 or POD6-24) after both intensive and less intensive frontline treatment. The prognostic performance of time until POD was replicated in an independent cohort of 245 patients with relapsed MCL, with median OS2 of 0.3 years (95% CI, 0.1-0.5) for PRF/POD6, 0.8 years (95% CI, 0.6-0.9) for POD6-24, and 2.4 years (95% CI 2.1-2.7) for POD>24. Early POD is associated with inferior OS2 in patients with relapsed MCL, identifying a high-risk population for future prospective studies.