OBJECTIVE: To determine whether IVF or a standard infertility treatment algorithm results in better outcome and/or lower cost when used as first-line therapy for couples with infertility. DESIGN: Prospective, randomized clinical study. SETTING: University-affiliated infertility clinic. PATIENT(S): Couples with newly diagnosed infertility and no prior treatment. INTERVENTION(S): Couples were randomized to undergo either IVF (group 1, n = 46) or a standard infertility treatment algorithm (group 2, n = 50) as initial therapy for infertility. MAIN OUTCOME MEASURE(S): Pregnancy rates and costs per couple, per month of treatment, and per pregnancy. RESULT(S): Pregnancy rates were higher in group 2 than in group 1. Costs per couple were not statistically different, although a trend toward higher costs was apparent in group 1, reflected by a higher median cost per clinical pregnancy established and a higher cost per month of treatment. Whereas cost differences between the groups diminished over time, pregnancy rates remained the same. CONCLUSION(S): In vitro fertilization currently does not represent an appropriate first-line treatment option for couples with infertility. The use of a standard infertility treatment algorithm results in a higher pregnancy rate and lower cost and therefore should be the preferred treatment approach.