To systematically review available data on the effect of daily medication dosing frequency on medication adherence in chronic disease states, as assessed by precise medication event monitoring systems (MEMS). Systematic review of relevant literature published between January 1986 and August 2007. Four electronic databases were searched to identify appropriate studies. Study selection criteria included prospective study design, patient population with quiescent chronic disease, medication intervention prescribed to each treatment arm for at least 6 weeks, and the use of MEMS to measure adherence. Data were extracted on the chronic disease being treated, the frequency of medication dosing, and the proportion of days with correct number of doses. Twenty studies met the selection criteria. All studies reported higher adherence rates in patients using less frequently dosed medications, and these differences were statistically significant (P <.05) in 75% (15 of 20) of studies. For 5 of 6 studies comparing once-daily versus thrice-daily dosing, patients receiving once-daily dosing had 22% to 41% more adherent days compared with patients receiving thrice-daily dosing. For studies comparing once-daily versus twice-daily dosing, patients receiving once-daily dosing had 2% to 44% more adherent days compared with patients receiving twice-daily dosing, with most studies clustering around 13% to 26%. Patients are more compliant with once-daily compared with twice-daily or thrice-daily treatment regimens.