Introduction: Dental caries is a chronic complex disease of multifactorial etiology that affects a quarter of U.S. children. This study evaluated the association between prenatal smoking and offspring caries experience and used a negative control exposure analysis to assess if the association is causal. Methods: Data from 1429 mother-offspring participants of the 1991/92 Avon Longitudinal Study of Parents and Children conducted in Bristol, England were analyzed. Prenatal smoking (yes v. no) and quantity smoked (none, <half pack, ≥half pack) were self-reported while offspring caries experience was determined by clinical oral examinations at 3 time points. Discrete time hazards regression estimated hazard odds of first occurrence of offspring caries, and substituted partner smoking for prenatal smoking in a negative control exposure analysis. Results: Overall, 22% smoked during pregnancy while 36% of partners smoked. The adjusted hazard odds of first occurrence of caries experience in the offsprings of prenatal smokers compared to the offsprings of non-smokers was 1.42 (95% CI: 1.08, 1.86). Relative to non-smoking, smoking <half pack/day and ≥half pack/day during pregnancy were associated with higher adjusted hazard odds of offspring caries experience: 1.10 (95% CI: 0.79, 1.54) and 1.38 (0.98, 1.95) respectively. Partner smoking was associated with 33% (95% CI: 1.07, 1.65) higher adjusted hazard odds of first offspring caries experience occurrence. Conclusions: Prenatal and partner smoking appear associated with greater offspring caries experience. The positive association with partner smoking suggests either a shared genetic predisposition or unmeasured common environmental factors with the mother as opposed to a direct biological effect of the intrauterine environment.