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Aim This exploratory post hoc analysis of a randomized, double‐blind (DB), multicentre, non‐inferiority study (NCT01515423) evaluated the effects of the long‐acting injectable antipsychotic therapies once‐monthly paliperidone palmitate (PP1M) and once‐every‐3‐months paliperidone palmitate (PP3M) on symptom severity and functional remission in patients with schizophrenia with differing durations of illness (≤5, 6‐10 and >10 years). Methods Endpoints included Personal and Social Performance (PSP) scale and Positive and Negative Syndrome Scale (PANSS) total scores during the DB phase (DB baseline and DB endpoint) and the proportion of patients meeting PSP or PANSS remission criteria at any time during the open‐label (OL) or DB phases that were maintained for ≥3, ≥6, ≥9 or ≥12 months. Results In both the OL and DB phases, significant improvements in PSP scale and PANSS scores were observed from baseline in all duration‐of‐illness groups, with significantly greater improvements observed in the ≤5‐year and 6‐10‐year groups compared with the >10‐year group. The proportion of patients who maintained PSP or PANSS remission criteria for ≥3, ≥6, ≥9 and ≥12 months was higher in the ≤5‐year and 6‐10‐year groups than in the >10‐year group. Safety profiles were similar across duration‐of‐illness groups in the DB phase. Conclusions Symptomatic and functional improvements were observed with PP1M/PP3M in patients with differing durations of schizophrenia, but the magnitude of the effects was greater in those with early illness vs chronic illness. These findings advocate implementation of PP1M and PP3M in all stages of schizophrenia, including early illness.