Background <p>In January 2025, China advanced the recommended first pertussis vaccine dose from 3 to 2 months of age. We evaluated the real-world effectiveness and safety of 2-month initiation, which was already practised via pentavalent vaccine schedules prior to the policy change, and assessed the impact of dosing timeliness on pertussis risk.</p> Methods <p>This retrospective birth cohort study linked immunisation, disease surveillance, and adverse event databases in Chongqing, China. Infants born between September 1, 2023, and March 1, 2024, who completed an unmixed three-dose primary series of pertussis-containing combination vaccine were followed until September 1, 2024. We compared 2-month with 3-month initiation for pertussis incidence and adverse events following immunisation (AEFI); infants initiating at other ages (9.3%) or infected before dose 1 were excluded from effectiveness analyses.</p> Findings <p>Among 76,844 eligible infants, 2-month initiation reduced the pre-vaccination infection window: pertussis before dose 1 occurred in 3 (0.02%) versus 38 (0.07%) in the 3-month group. Of 69,612 infants in effectiveness analyses (13,815 and 55,797 in the 2-month and 3-month groups, respectively), post-primary series incidence was similar between groups (6.99 versus 6.80 per 1000 person-years). Timely inter-dose intervals were associated with lower pertussis risk regardless of initiation age (3.99 versus 10.66 per 1000 person-years for on-time versus non-adherent schedules), regardless of initiation age. AEFI were rare (0.34%) and comparable between groups, with no serious vaccine-related events.</p> Interpretation <p>Two-month initiation provides equivalent protection and safety while narrowing the vulnerable pre-vaccination window. Timely inter-dose intervals are as critical as early initiation, a finding with global relevance. These data support China’s 2025 policy change.</p>