Background Although mother’s own milk decreases prematurity-associated morbidities, mothers of infants born preterm and very low birth weight experience a significantly shorter lactation duration. Little is known regarding factors associated with lactation cessation during the hospitalization of a very low birth weight infant. Research aim To determine demographic, social, and personal factors associated with lactation cessation by 6-weeks postpartum in mothers delivering very low birth weight infants. Methods We used a retrospective, longitudinal, two-group comparison design using data from a randomized control study. Mothers of very low birth weight infants ( N = 142) were enrolled from a labor and delivery unit associated with a Level 4 neonatal intensive care unit. Demographic, social, and health information was obtained from the medical records. Participants were surveyed regarding lactation goals, experience, and reason(s) for cessation. Results Participants who did not continue lactating for more than 6 weeks were more likely to be unemployed ( p = .019), Medicaid eligible ( p = .009), less educated ( p < .031), smoke ( p = .002), provide less skin-to-skin care ( p = .007), and to delay the decision to provide their milk to their infant ( p = .007). After Bonferroni adjustment, only minutes of skin-to-skin care remained statistically significant. Insufficient maternal milk production was the most common reason for lactation cessation. Conclusion While the etiology of lactation cessation is often non-modifiable, strategies aimed at maintaining mother’s own milk production, smoking cessation, increasing skin-to-skin care, and promoting an earlier decision to lactate, may prolong lactation duration in this vulnerable population. This RCT was registered (2012-00071) with ClinicalTrials.com on 6/28/2013.