BACKGROUND: The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) alongside long-lasting insecticide-treated nets (LLIN) and case management for reducing the risks associated with malaria in pregnancy in areas of moderate-to-high transmission in sub-Saharan Africa. Due to increasing Plasmodium falciparum resistance to SP, the search for alternative drugs or strategies to control malaria in pregnancy is a priority. We assessed the acceptability among pregnant women and health providers of intermittent screening and treatment (ISTp) and IPTp with dihydroartemisinin-piperaquine (DP) as alternative strategies in the context of an un-blinded clinical trial. METHODS: Qualitative data were collected through ten focus group discussions with women participating in a randomized controlled trial to evaluate ISTp or IPTp with DP (multi-day regimen) versus IPTp with SP (single dose) in western Kenya. Individual in-depth interviews were conducted with 26 health providers working in the trial facilities and trial staff. RESULTS: Women appreciated the advantages of being tested with a rapid diagnostic test (RDT) at every ANC visit (although a few women disliked finger pricks) and accepted that they would not receive any antimalarial when tested RDT-negative. There were differences in women's experiences of the efficacy of antimalarials between the trial arms, with more women in the IPTp-SP arm reporting they had experienced malaria episodes. Side effects were experienced among women taking DP and SP. Although women and trial staff reported adherence to the full DP regimen within the trial, health providers were not confident that women would adhere to multi-day regimens in non-trial settings. Health providers recognized the advantages of ISTp in reducing unnecessary exposure to drugs, but lacked confidence in the reliability of RDTs compared to microscopy. CONCLUSIONS: Our findings indicate that, within a trial context, ISTp-DP and IPTp-DP were generally acceptable among both users and providers and were regarded as potentially valuable alternatives to IPTp-SP. Several challenges were identified the most important of which was concerns with achieving adherence to DP in non-trial settings, requiring operational feasibility studies in routine health systems. Policy adoption of ISTp with RDTs would require a major shift in thinking among health providers due to lack of confidence in RDTs.