Here we present the characterization and comparison of miRNome of drought tolerant (N22) and sensitive (PB1) indica rice cultivars under natural as well as field drought conditions. Both cultivars displayed apparent tissue biased expression of miRNAs. Comparative analysis of miRNA abundance from different tissue (flag leaf, panicle and root) of both the varieties identified 36 and 10 flag-leaf-enriched miRNAs, 14 and 42 spikelet-enriched miRNAs and 13 and 13 root enriched miRNAs in N22 and PB1, respectively. Further the flag leaf of N22 outshines among spikelet and root as huge number of miRNAs were differentially regulated under drought suggesting the crucial role of flag leaf in drought tolerant N22. A total of 80 miRNAs (16/64 up-/down-regulated) in flag leaf, 19 miRNAs (2/17 up-/down-regulated) in spikelet and 38 miRNAs (24/14 up-/down-regulated) in roots were differentially regulated under drought in N22. While 28 miRNAs (9/19 up-/down-regulated) in flag leaf and 31 miRNAs (11/20 up-/down-regulated) in spikelets were observed to be drought responsive in PB1. Similarly,, a total of 66 miRNAs (34/32 up-/down-regulated) were differentially regulated in the spikelets from heading to anthesis stage. In addition 69 miRNAs (30/39 up-/down-regulated) showed drought-mediated regulation in spikelets of N22 at anthesis stage.