The experiment was conducted at Spices Research Centre, Shibganj, Bogra, Bangladesh during kharif season 2013-14 and continued in 2014-15 to determine optimum dose of N, P and K in combination with organic & inorganic source and to assess the effect of N, P and K on the yield and quality of betel leaf. The land was medium high and the soil was silty loam in texture. The experiment was laid out in a Randomized Complete Block Design (RCBD) with three replications. Different fertilizer doses viz. N = 0, 50, 100, 150 kg ha-1, P = 0, 22, 44 kg ha-1 and K= 0, 21, 42 kg ha-1 were considered as treatment. The treatment combinations were T1 = N0P0K0, T2 = N0P22K21, T3 = N50P22K21, T4 = N100P22K21, T5 = N150P22K21, T6 = N150P44K21, T7 = N150P44K42, T8 = N100P0K21, T9 = N100P44K21, T10 = N100P22K0 and T11 = N100P22K42. The total amount of N as per treatment was top dressed in 8 equal splits at 45 days’ interval. The sources of N were 50% from Urea and 50% from mustard oil cake. Betel leaf advanced line BL-018 was used as a test crop. The highest leaf yield (59000 bira ha-1 in 2013-14 & 142200 bira ha-1 in 2014-15) was obtained from the treatment T11 = N100P22K42 which was identical to T9 = N100P44K21 (55370 bira ha-1 in 2013-14 & 123500 bira ha-1 in 2014-15) and T4 = N100P22K21 (51590 bira ha-1 in 2013-14 & 120600 bira ha-1 in 2014-15). The lowest leaf yield (26030 bira ha-1 in 2013-14 & 57090 bira ha-1 in 2014-15) was recorded from T1 = N0P0K0 (1 bira= 80 leaves). It was concluded that N100P22K42, N100P44K21 and N100P22K21 kg ha-1may be the good alternative for betel leaf cultivation where 50% N was supplied from urea and 50% from mustard oil cake. Among them N100P22K42 kg ha-1would be the best due to less disease infestation, higher productivity and higher economic return.