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Background: Pertussis remains poorly controlled relative to other diseases targeted by childhood vaccination programs. We combined estimates from four population-based studies of pertussis vaccine effectiveness (VE) in three Canadian provinces using a meta-analytic approach to improve precision and explore regional variation in VE and durability of protection., Methods: Studies were conducted in Alberta, Manitoba, and Ontario over periods ranging from 1996 to 2015. Adjusted log odds ratios (OR; VE = 100*[1-OR]) of the effect of vaccination on pertussis risk were estimated by time since last vaccination in each study and pooled using DerSimonian and Laird random-effects models. We used the I 2 statistic to estimate between-study heterogeneity and assessed methodological and clinical heterogeneity through subgroup analyses of study design and age., Results: Data on 3,270 pertussis cases and 23,863 controls were available. Pertussis VE declined from 86% (95% CI 79%-90%, I 2  = 81.5%) at < 1 year since last vaccination to 51% (11%-74%, I 2  = 80.9%) by ≥ 8 years. Effect estimates were the most heterogeneous in the least and most elapsed time periods since last vaccine dose. This was attributable mostly to variation between provinces in the distribution of age groups and number of vaccine doses received within time periods, as well as study design and small numbers in the most elapsed time period., Interpretation: Consistent trends of decreasing pertussis VE with increasing time since last vaccination across three Canadian provinces indicate the need for immunization schedules and vaccine development to optimize protection for all individuals, especially for adolescents and young adults at greatest risk of infection., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CHR has received an unrestricted research grant from Pfizer for an unrelated study. SMM has received unrestricted research grants from Merck, GlaxoSmithKline, Sanofi Pasteur, Pfizer and Roche-Assurex for unrelated studies, as well as fees as an advisory board member for Sanofi Pasteur., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)