Garlic(Allium sativum L.) is one of the important vegetable crop in Ethiopia. However, the yield of the crop is constrained by low and imbalanced nutrient supply in to the soil. Therefore, this field experiment has been conducted in Lay Gayint district in the year of 2016/2017 using irrigation with the objective of enhancing garlic productivity and production by using integrated NPS fertilizer and cattle manure in the Highlands of Ethiopia. The treatments were the combinations of four levels of NPS (0-0-0; 52.66-45.98-8.4; 105.32-91.96-16.94 and 157.98-137.94-25.34 kg ha-1) and four levels of manure (0, 5, 10 and 15 t ha-1), and laid out in a randomized complete block design (RCBD) with three replications. Data were collected on phenology, vegetative and yield related of garlic crop and analyzed using SAS (2002)9.1.3 version. Most of the growth and yield parameters were significantly (P<0.01 & P<0.05) affected by main and interaction effects of cattle manure and NPS fertilizer. Non fertilized plants in the control treatment were inferior in all parameters. The results in both main and combined effect of CM and NPS mineral fertilizer didn't have indeed significant effects on days to emergence. Whereas, both CM and NPS fertilizer significantly (P<0.01) affected maturity date of garlic. In the combined effect, Significantly highest plant height (73cm), leaf number(10 ), leaf length (65.4cm) and neck diameter(1.08cm), BD(4.79cm), BW(55.45t/ha), MBW(17.35t/ha) and TBY(18.03t/ha) were recorded in the combined application of 10t/ha CM and 105.32-91.96-16.94kgha-1 NPS fertilizer followed by BD(4.48cm),CN(9.2),BW(52.6tha-1), MBW(17.13T/ha) and TBY(17.16) plants supplied with 15t/ha CM and 52.66-45.98-8.4kgha-1 NPS fertilizer. Even though treatment11 were highly significant in almost all growth and yield parameter, According to marginal rate of return garlic plants (T10) that received 10tha-1 CM and52.66-45.98-8.4kgha-1 NPS fertilizer were scored the first with MRR% of 20355.04(479293.50 ET Birr Net benefit) that can be recommended to increase garlic productivity and production to small holder farmers around the study area at lay Gayint district. However, study has to be done under varies seasons across location to give a concessive recommendation. KEY WORDS: Garlic, Cattle manure, Main Effect, Combined Effect, Marginal rate of