The parasitic weed Striga affects maize on 20 million ha in Africa and contributes significantly to its low productivity there (1.3 t/ha versus the world average of 4.2 t/ha). A single Striga plant produces over 50,000 seeds that remain viable in soil for up to 20 years. CIMMYT and partners have developed a technology that combines low doses (<30 g/ha) of imazapyrŪ herbicide applied as a seed coating to non-transgenic Imidazolinone resistant (IR) maize, thereby controlling Striga before or during attachment to maize roots. We evaluated 22 CIMMYT open-pollinated IR varieties (OPVs) for mid-altitude ecologies of Eastern and Central Africa at 10 Striga-free and 12 infested sites in 4 countries. Under Striga infestation, the best IR-OPV yielded twice as much (2.6 vs. 1.3 t/ha) as the best check. Seventeen IR-OPVs had 62-144% higher grain yield than KSTP94, the commercial, Striga tolerant check. Two IR-OPVs significantly out-yielded the tolerant commercial check under Striga-free conditions. Striga density averaged 1 plant/m2 on the IR-OPVs and 5 plants/m2 on the checks across environments. The correlation between Striga plants/m2 and grain yield was low but significant (r = -0.22, P<0.001). There were highly significant (P<0.001) genotype and genotype x environment interactions (GxE) for Striga plants/m2 and grain yield, implying varying efficacy of the IR practice across environments. GxE accounted for 19% of the total variation in Striga plants/m2. Significant GxE for Striga emergence underscores the need for multilocational testing to verify the viability of the IR practice and to adapt it to diverse production settings in sub-Saharan Africa.