Iron deficiency (ID) is prevalent among infants world-wide and may be more likely among infants born to women living in disadvantaged environments. A strategy to address ID in this context is to feed iron-fortified formula, but this may create risk for gastrointestinal (GI) infection. Our objective was to investigate the relationship between infant feeding practices, iron status, and likelihood of a GI infection in the first 6 mo of life. We conducted a prospective study at a public hospital in Guadalajara, Mexico. Healthy women who gave birth to a healthy term infant were eligible to participate. Each month, mothers (n = 154) provided information on infant feeding methods and symptoms of GI infection. At 6 mo of age, infants' iron status was assessed [hemoglobin (Hb) and serum ferritin concentration]. When compared with nonpredominantly breast-fed [partially breast-feeding (PBF) and formula feeding (FF) combined], predominantly breast-fed (PRBF) infants to 6 mo had a lower incidence of GI infection from 0-6 mo [18 vs. 33%; P = 0.04; adjusted odds ratio (OR) = 0.4; 95% CI = 0.2, 1.0] but a higher risk for ID (serum ferritin < 12 microg/L) at 6 mo (22 vs. 4%; P = 0.001; adjusted OR = 9.2; 95% CI = 2.3, 37.0). Anemia (Hb < 110 g/L) prevalence did not differ among feeding groups (13% for PRBF, 19% for PBF, and 4% for FF; P = 0.09). In this low-income population, our results suggest that PRBF should be promoted and the risk for ID managed using public health and nutrition strategies.