We examined short- and long-term effects of high milking frequency (HMF) for the first 21 days of lactation. The study included 122 Israeli Holstein cows – 32 pregnant heifers, 40 cows in second lactation and 50 cows in >second lactation. Heifers were paired according to predicted transmitting ability and cows according to energy-corrected milk (ECM) production, age, days in milk and expected calving date. Thin cows (body condition score <2.75) were not included. One cow from each pair was arbitrarily allocated to a control group milked three times daily (3× milking cows) and the counterpart to an experimental group milked six times daily for the first 21 days of lactation and then three times daily for the rest of the lactation (6× milking cows). During the first 21 days of lactation, 6× milking cows produced 9.3 kg more milk (26.5%) and 7.16 kg more ECM (19%) than the 3× milking cows. The higher milk production persisted throughout the entire lactation (305 days), as reflected by treatment×age interaction showing higher milk production for the first and second (7%) but not >second lactation cows relative to their control counterparts (−0.37%); ECM production was also higher in 6× milking first and second lactation (7.6% and 5%, respectively) but not for >second lactation cows. Furthermore, HMF had long-lasting effects, expressed as significantly higher milk production through the succeeding lactation in the previous first lactation cows (10%); a tendency toward significance in the second lactation cows relative to the controls (4.7%), but a deleterious effect on the >second lactation cows, reflected by lower milk production (−5.25%) than in controls; similar patterns were found for the ECM. For the entire 305 days of lactation, fat and protein yields were higher for first and second lactation cows, whereas protein yield for >second lactation cows was lower in the 6× milking v. control group. Given that HMF during the first 21 days of first or second lactation increases milk and ECM yields throughout the concurrent and successive lactation with no adverse effect on energy balance, mastitis, metabolic diseases or reproduction, it seems to be economically beneficial. However, caution should be paid for >second lactation cows due to absence of significant effect in the entire of the first HMF applied lactation and the deleterious effect in the succeeding lactation.