Prenatal multivitamin supplements (PMS) are recommended during pregnancy. Suboptimal adherence in women experiencing gastrointestinal (GI) conditions is thought to be attributed to the high elemental iron content in PMS. This study sought to quantify adherence and tolerability of iron-containing PMS in women with pre-existing GI conditions by recruiting women who called the Motherisk Helpline. Women with (n = 36) and without (n = 166) pre-existing GI conditions were randomised to either PregVit (n = 106) or Orifer F (n = 96). Monthly follow-up interviews were conducted to assess pill intake and GI adverse effects associated with PMS. The results of our study suggest that with the use of small size and low dose iron PMS, women with pre-existing GI conditions do not experience (1) more GI adverse effects, (2) lower adherence than women with no such conditions, and (3) may experience less severe nausea and vomiting of pregnancy. Supplementing with small tablets of low dose iron PMS should be considered.