We performed a meta-analysis to compare the effects of feeding calcium salts of palm fatty acids (PFAD; ~50% C16:0 and ~50% unsaturated 18-carbon fatty acids) to a nonfat supplemented diet used as control on nutrient digestibility (n = 35) and production responses (n = 121) of lactating dairy cows. Furthermore, the interaction between PFAD supplementation and experimental design (crossover/Latin square [CL] vs. randomized as block or completely randomized [RD]) were examined. The database was formed from 35 peer-reviewed publications with PFAD supplemented at ≤3% diet DM. These publications comprised 13 CL and 22 RD studies. For the 35 digestibility observations, 18 were from CL and 17 from RD; for the 121 production observations, 41 were from CL and 80 from RD. The meta-analysis was performed using PROC MIXED of SAS, including fixed effects of treatment (PFAD and CONTROL), design, and the interaction between treatment and design. Studies were weighted based on the inverse of the sum of both the within and among study variance. We did not observe interactions between treatment and study design for any variable (all P > 0.30). Compared with control, PFAD reduced DMI (0.66 kg/d, P = 0.03) and milk protein content (0.05%, P = 0.04), and increased milk yield (1.42 kg/d, P = 0.02) and fat yield (0.08 kg/d, P < 0.01). There were no treatment differences for protein yield (P = 0.95) or milk fat content (P = 0.66). Although PFAD did not affect DM digestibility (P = 0.91), PFAD increased NDF digestibility (2.45% units; P < 0.01) compared with control. Compared with RD, CL increased DMI (2.14 kg/d, P = 0.05) and tended to increase fat yield (0.29 kg/d, P = 0.06). Study design did not affect any other variables (all P > 0.14). In conclusion, PFAD reduced DMI, increased the yields of milk and milk fat, decreased protein content, and increased NDF digestibility. We observed no interactions between study design and dietary treatment, indicating no reason for the restrictive use of crossover/Latin square designs in fat supplementation studies and meta-analysis.