Two experiments examined the effects of Aspergillus oryzae fermentation product (AO; Amaferm®; BioZyme Inc., St. Joseph, MO, USA) on productive variables in transition dairy cows. In experiment 1, 33 Holstein cows (22 multiparous and 11 primiparous) were enrolled from −21 to 60 days in milk (DIM). Cows were individually fed either a control total mixed ration (TMR) diet consisting of primarily alfalfa hay and steam-flaked corn [62:38 and 59:41, forage:concentrate (F:C) for prepartum and postpartum phases, respectively] or the control diet along with 15 g d−1 of AO. In experiment 2, 455 multiparous Holstein cows were enrolled from −21 to 121 DIM. Cows were group-fed either a control TMR diet (n = 228) consisting primarily of corn silage and rolled corn (44:56, F:C) or the control diet (n = 227) with 15 g d−1 of AO. In experiment 1, cows fed AO had increased (P < 0.05) milk production compared with controls (37.7 vs. 34.6 kg d−1). Milk composition, dry matter intake, body weight (BW), and BW loss both prepartum and postpartum did not differ (P > 0.10) between treatments. Cows fed AO tended to have decreased plasma nonesterified fatty acids levels (14%, P < 0.10), but plasma glucose concentration did not differ (P = 0.89). In experiment 2, cows fed AO had decreased milk yield (43.0 vs. 43.8; P < 0.05), and increased milk fat content (3.50% vs. 3.38%; P < 0.01) but similar quantities of 3.5% fat-corrected milk (42.5 vs. 42.7 kg d−1; P > 0.10). Results suggest that AO has the potential to improve aspects of milk production efficiency, but the percentage and types of forage utilized may influence the response.