This study aimed to evaluate the effect of using synthetic liquid milk (LM) in combination with whole cow milk (WCM) in replacing of the whole buffalo milk (WBM) during pre-weaning on growth performance of buffalo calves during post weaning. Twelve newly born buffalo calves (9 males and 3 females) were divided randomly according to their body weight and sex into three similar groups with average body weight 42.13 kg at the beginning of the first part of this study which published by Mona et al. (2014). Mean live body weight at the beginning of the 2nd experiment was 100.51, 98.16 and 92.63 kg and aged 98, 105 and 84 days at weaning of treatments G1: 100% of allowances from WBM (control), G2: 75% of allowances from WCM plus 25% LM, and G3: 50% of allowances from WCM plus 50% LM had given during pre-weaning period in the first experimental. Over the 2nd experiment all animal groups were fed according to Kearl (1982), concentrate feed mixture (CFM 1) (16% CP and 70%TDN), berseem hay and rice straw (70: 25: 5%) from weaning weight up to 150 kg of live body weight (1st period) and fed concentrate fed mixture (CFM 2) (14% CP and65% TDN), berseem hay and rice straw (60: 25: 15%) from 150 kg up to 250 kg of live body weight (2nd period).Results indicated that during the 1st period of post weaning, G3 recorded significant higher (P<0.05) daily feed intake as DMI and TDN, digestibility of DM and CP, total gain and daily gain than those of other treatments. While those fed G3 or (G2) recorded significant higher CF digestibility than those in (G1). On the other hand, G2 showed the longest period at age during the first period. Concerning the results during the 2nd period at post weaning, there were no significant differences among treatments respecting daily feed intake, feed conversion, digestibility coefficients, live body weight and daily gain. Also, calves in G3 showed the shortest period of age in second period, while the animals fed G1 showed that the highest (P<0.05) values of total gain, and the lowest one was recorded for G2 ration. Data of economic efficiency during overall experimental period indicated that the most expensive daily feeding cost was recorded for group G3 or G1, compared with G2. While, price of daily weight gain of calves fed G3 or G1 were higher than those of G2 group. The same trend respecting relative return and economic efficiency was found. The best relative return and economic efficiency were obtained by calves fed G3, followed by G1, while G2 recorded the lowest return and economic efficiency. This may help farmers to keep up and care of suckling buffalo calves and not sell them and such regime could help to alleviate the problem of milk and beef shortage in Egypt.