["Addiction, Volume 121, Issue 5, Page 1112-1127, May 2026. ", "\nAbstract\n\nAims\nAs clinical trial evidence on the effectiveness of smoking cessation pharmacotherapies during pregnancy is inconclusive, we conducted a large cohort study examining their effectiveness and comparative effectiveness during pregnancy.\n\n\nDesign\nPopulation‐based cohort study. We used propensity score matching and conditional Poisson regression to compare pharmacotherapy‐exposed with unexposed pregnancies, and to compare varenicline‐exposed with nicotine replacement therapy (NRT) ‐exposed pregnancies.\n\n\nSetting\nBirth records (2005–2020) from New South Wales (NSW) Australia, New Zealand (NZ) and Norway/Sweden linked to pharmacotherapy dispensing records.\n\n\nParticipants/cases\nWomen with a birth record indicating smoking in early pregnancy [during first 20 weeks' gestation (NSW), at lead maternity registration (NZ) or during the first trimester (Norway/Sweden)]. Participants were dispensed prescription NRT, varenicline or bupropion in the first 18 weeks of gestation (NSW, Norway/Sweden) or between the first antenatal visit and childbirth (NZ).\n\n\nMeasurements\nWe defined smoking cessation as not smoking after gestational week 20 (NSW), at gestational week 32–36 (Norway/Sweden) and at two weeks postpartum (NZ), identified via self‐report and documented in the birth record.\n\n\nFindings\nOur NRT analyses included 623, 7074 and 70 exposed and 6026, 68 161 and 700 propensity‐score‐matched unexposed pregnancies from NSW, NZ and Norway/Sweden, respectively. The associations between NRT and smoking cessation were mixed but tended toward reduced cessation compared with no pharmacotherapy. In NSW, NRT was associated with a reduction in cessation [relative risk (RR) = 0.68, 95% confidence interval (CI) = 0.48–0.97], while in NZ, the effect was smaller (RR = 0.93, 95% CI = 0.89–0.98) but inconclusive in Norway/Sweden (RR = 0.91, 95% CI = 0.61–1.35). Smoking cessation was also equally or less common among varenicline‐exposed pregnancies (NSW: 308 exposed vs 3077 matched unexposed, RR = 0.89, 95% CI = 0.72–1.09, Norway/Sweden: 196 exposed vs 1960 matched unexposed, RR = 0.49, 95% CI = 0.34–0.70). Our comparison of varenicline‐exposed with NRT‐exposed pregnancies indicated increased smoking cessation among varenicline‐exposed pregnancies (NSW: 108 vs 154 exposed, RR = 1.91, 95% CI = 1.10–3.22). There were too few bupropion‐exposed pregnancies to support interpretation.\n\n\nConclusions\nVarenicline appears to be more effective at smoking cessation than nicotine replacement therapy during pregnancy. The uncertainty about the real‐world effectiveness of nicotine replacement therapy and bupropion remains as this study's analyses were impacted by non‐adherence and biased by unmeasured confounding.\n\n"]