To explore the prevalence and risk factors of infertility in Iran, a total of 12 285 ever-married women aged 15–50 years old and their husbands (if available) were interviewed by 82 female general practitioners and answered a self-administered questionnaire on several aspects of infertility. They were identified from the national population in 30 counties, and invited to a confidential interview. Data were obtained about their age, education, marital status, toxic habits, medical history, disabilities and illnesses, help-seeking, economy, ethnicity, geographic location, contraceptive use and age at which they had first intercourse. This study used the definition of childlessness proposed by World Health Organization: ‘the woman has never conceived despite cohabitation and exposure to pregnancy for a period of 2 years’. The overall prevalence of infertility was 8% (95% CI: 3.2–15.0). The weighted national estimate of primary infertility was 4.6% (95% CI: 3.6–5.2). There was a pronounced regional pattern in the levels of primary infertility. The primary infertility increased significantly from 2.6 to 4.3 to 5.5% for the 1985–1989, 1990–1994 and 1995–2000 marriage cohorts. The prevalence of secondary infertility was 3.4% (95% CI: 2.4–5.1). Overall the prevalence of infertility falls within a relatively wide range being high in the Southern counties, and low in the Northern counties. The probability of first pregnancy at the end of 2 years of marriage was 0.78 for all ever-married women. The prevalence of infertility increased with age (linear chi-square 198.012, 1 d.f., p = 0.01). The age pattern of infertility also varies quite markedly across the counties analysed. No effect of race was detected; neither the intercept (analysis of covariance p = 0.36) nor the slope of the age relationship was influenced by race (analysis of covariance p = 0.41). Infertility were observed as significantly higher in the presence of history of tubo-ovarian surgery [odds ratio (OR): 1.43; 95% CI: 1.28–2.23; p = 0.01], salpingitis (OR: 2.34; 95% CI: 1.31–4.3; p = 0.016), ectopic pregnancy (OR: 2.45; 95% CI: 1.90–3.44; p = 0.04), varicocele (OR: 2.85; 95% CI: 1.61–5.20; p = 0.01) and cryptorchidism (OR: 3.81; 95% CI: 2.51–4.28; p = 0.031). This study provides a quantitative estimate of the prevalence and main risk factors for infertility in Iranian couples. Yet, further studies on the cause of primary and secondary infertility and geographical variations in the incidence and prevalence of infertility in Iran are needed.