Objective. The objective of this study is to examine the effect of country-specific EQ-5D preference weights on the cost-effectiveness (CE) of initial pramipexole versus levodopa strategy in patients with Parkinson disease (PD). Methods. A total of 301 subjects with PD were randomized to initial pramipexole or levodopa and followed every 3 months over a 4-year period. Subjects' health-related quality of life (HRQOL) was measured using EQ-5D, and their health preferences were calculated using both the UK and US sets of weights. The effectiveness of pramipexole was defined as the additional quality-adjusted life-years (QALY) gained compared to levodopa and was estimated as the area between the treatment-specific HRQOL profiles adjusted for baseline difference. Results. Using the original UK weights, the incremental effectiveness was 0.155 QALYs, which resulted in the incremental CE ratio (ICER) of $42,989/QALY and a probability that pramipexole was cost-effective relative to levodopa of 0.57, 0.77, and 0.82 when a QALY was valued at $50,000, $100,000, and $150,000, respectively. Using the US-specific weights resulted in lower incremental effectiveness (0.062 QALYs), higher ICER ($108,498/QALY), and a lower probability that pramipexole was cost-effective compared to levodopa at any valuation of QALY (0.23 for $50,000, 0.48 for $100,000, and 0.58 for $150,000). Conclusions. Country-specific preference weights in clinical-economic trials might have important effects on estimates of incremental cost-effectiveness. Using US preference weights rather than UK preference weights reduced the probability that pramipexole was cost-effective compared to levodopa.