IMPORTANCE Bottle feeding has been implicated in the etiology of hypertrophic pyloric stenosis (HPS). Further data are needed to define the nature of this relationship and the clinical variables that influence it. OBJECTIVE To determine if bottle feeding after birth is associated with the development of HPS in infants. We hypothesized that bottle feeding is associated with an increased risk of HPS and that this risk is modified by other risk factors. DESIGN, SETTING, AND PARTICIPANTS Population-based case-control study of births from January 1, 2003, to December 31, 2009, using Washington State birth certificates linked to hospital discharge data. Cases included all singleton infants born within the study period and subsequently admitted with both a diagnostic code for HPS and a procedure code for pyloromyotomy (n = 714). Controls were randomly chosen among singleton infants who did not develop HPS and were frequency matched to cases by birth year. EXPOSURE Feeding status (breast vs bottle) was coded on the birth certificate as the type of feeding the infant was receiving at birth discharge. MAIN OUTCOME AND MEASURE Diagnosis of HPS. RESULTS Hypertrophic pyloric stenosis incidence decreased over time, from 14 per 10,000 births in 2003 to 9 per 10,000 in 2009. Simultaneously, breastfeeding prevalence increased from 80% in 2003 to 94% in 2009. Compared with controls, cases were more likely to be bottle feeding after birth (19.5% vs 9.1%). After adjustment, bottle feeding was associated with an increased risk of HPS (odds ratio [OR], 2.31; 95% CI, 1.81-2.95). This association did not differ according to sex or maternal smoking status but was significantly modified by maternal age (<20 years OR, 0.98; 95% CI, 0.51-1.88; ≥35 years OR, 6.07; 95% CI, 2.81-13.10) and parity (nulliparous OR, 1.60; 95% CI, 1.07-2.38; multiparous OR, 3.42; 95% CI, 2.23-5.24). CONCLUSIONS AND RELEVANCE Bottle feeding is associated with an increased risk of HPS, and this effect seems to be most important in older and multiparous women. These data suggest that bottle feeding may play a role in HPS etiology, and further investigations may help to elucidate the mechanisms underlying the observed effect modification by age and parity.