The optimal way of oral iron replacement for iron deficiency anaemia(IDA) is still unknown and few recent studies have reported better fractional absorption and tolerability of intermittently administered iron. This randomised, active comparator controlled, open-label trial evaluated efficacy and tolerability of 120 mg elemental iron (2 × 200 mg ferrous sulphate tablets) administered as a single dose on alternate days (alternate-day arm, ADA) vis-à-vis 60 mg elemental iron (single FeSO tablet) administered daily (daily arm, DA), among women (age ≥ 18 years) having IDA, with haemoglobin (Hb) concentration between 6 and 10 g/dL and serum ferritin < 30 µg/L. Primary outcome was the Hb change on Day-28. Secondary outcomes included Hb change on Day-56, change in serum hepcidin levels from baseline to Day-14, adverse effects (AEs) and compliance to treatment. Sixty-eight participants (34 each in DA and ADA) were enrolled in the trial. Hb change at Day-28 was significantly higher in the ADA compared to DA (mean change: +2.2 ± 1.3 vs. +1.3 ± 1.1 g/dL,  = 0.003). Though Hb increment at Day-56 was also higher in ADA, it was not statistically significant. There was no significant difference in changes in serum hepcidin from baseline to Day-14 between the arms. Significantly higher proportion in the DA had AEs compared to ADA (45% vs. 9%,  < 0.005). However, treatment compliance was not significantly different between the arms. Alternate-day oral iron replacement led to significantly higher haemoglobin increment in the short run and caused significantly lesser AEs compared to daily replacement. Larger multicentric RCTs with longer duration of intervention should evaluate alternate-day replacement vis-à-vis daily therapy in future. This randomised controlled trial has been registered in Clinical Trial Registry-India (CTRI Reg. No.: , dated 2nd December 2021).