Objective To compare early and late responses to highly active antiretroviral therapy (HAART) in European and non‐European HIV‐1 infected patients in a Dutch cohort. Methods We retrospectively analysed the response to HAART of 216 previously treatment‐naive HIV‐1‐infected patients using the University Medical Centre Utrecht HIV database. African ( n =51), Asian ( n =7), and Central/South American ( n =6) patients were classified as non‐European, and others as European ( n =152). Early failure was defined as a viral load that remained above 400 HIV‐1 RNA copies/mL after 6 months of treatment with HAART. Late‐phase failure was determined in patients who were successfully treated in the early phase and was defined as two consecutive viral load measurements above 400 copies/mL, a new AIDS‐defining event or death. Results In the early phase, four of 152 (2.6%) European and eight of 64 (12.5%) non‐European patients failed HAART. A significant increased risk of virological failure in the early phase of treatment was observed for non‐Europeans as compared to Europeans (odds ratio 4.6; 95% confidence interval 1.1–20.2). Low serum drug levels in the absence of resistant virus were often seen at the time of early failure. No difference in late‐phase failure was observed between the two groups (adjusted hazard ratio 0.6; 95% confidence interval 0.3–1.2). Conclusions Non‐European patients had a 4.6 times higher risk of virological failure than their European counterparts in the first 6 months of treatment with HAART. This failure seemed to be associated with low serum drug levels at the time of failure. However, if HAART was successful in the early phase, response rates in the late phase were similar for Europeans and non‐Europeans.