OBJECTIVES: To assess the impact of reducing the frequency of oral therapies from multiple-dosing schedules to a once-daily (od) dosing schedule on adherence, compliance, and the associated economic impact. METHODS: All relevant studies were searched using electronic databases (MEDLINE® and Embase®). The studies assessing adherence with od, twice-daily (bid), thrice-daily (tid), and four-times daily (qid) dosing schedules, and costs associated with optimal/suboptimal adherence among patients with acute and chronic diseases, were included. There was no restriction on the treatments assessed other than that they were delivered orally. Comparisons of effect estimates across studies were pooled and analyzed using a DerSimonian and Laird random-effects model. RESULTS: Forty-three studies met the inclusion criteria of the review, of which 33 studies compared once-daily dosing schedule with multiple-dosing schedules. Data on adherence and compliance were available for studies in depression, HIV, hypertension, and respiratory tract infections (RTIs). Among these conditions, the overall results indicated that od schedule was associated with higher adherence rates [Odds Ratio (OR): 2.34; 95% Confidence Interval (CI): 1.31, 4.17; p=0.004 for od versus bid/tid dosing] and compliance rates (OR: 5.76; 95% CI: 1.89, 17.57; p<0.001 for od versus bid dosing) compared with multiple-dosing schedules. From a health economic perspective, it was observed that higher adherence rates with od schedule (relative to multiple-dosing schedules) prescribed in cardiovascular disorders, renal transplant, pain, RTIs, and ulcerative colitis were associated with lower costs of healthcare resource utilization. For example, treatment costs in renal transplant patients demonstrated total, per-patient cost savings of $9411 over a 5-year time horizon with od regimen compared with bid regimen. CONCLUSIONS: The present evidence base suggests that reducing the dose frequency from multiple dosing to once-daily dosing schedule could improve adherence and compliance among patients with acute and chronic diseases. Improving adherence was associated with further decreases in health care costs.