Abstract Background Kenya recently changed its antimalarial drug policy to a specific artemisinin-based combination therapy (ACT), artemether-lumefantrine (AL). New national guidelines on the diagnosis, treatment and prevention were developed and disseminated to health workers together with in-service training. Methods Between January and March 2007, 36 in-depth interviews were conducted in five rural districts with health workers who attended in-service training and were non-adherent to the new guidelines. A further 20 interviews were undertaken with training facilitators and members of District Health Management Teams (DHMTs) to explore reasons underlying health workers' non-adherence. Results Health workers generally perceived AL as being tolerable and efficacious as compared to amodiaquine and sulphadoxine-pyremethamine. However, a number of key reasons for non-adherence were identified. Insufficient supply of AL was a major issue and hence fears of stock outs and concern about AL costs was an impediment to AL prescription. Training messages that contradicted the recommended guidelines also led to health worker non-adherence, compounded by a lack of follow-up supervision. In addition, the availability of non-recommended antimalarials such as amodiaquine caused prescription confusion. Some health workers and DHMT members maintained that shortage of staff had resulted in increased patient caseload affecting the delivery of the desirable quality of care and adherence to guidelines. Conclusion The introduction of free efficacious ACTs in the public health sector in Kenya and other countries has major potential public health benefits for Africa. These may not be realized if provider prescription practices do not conform to the recommended treatment guidelines. It is essential that high quality training, drug supply and supervision work synergistically to ensure appropriate case management.