At peripheral health facility levels, the diagnosis of malaria is difficult due to lack of infrastructure. In the study reported here, the diagnostic performance of a batch of 'DiaMed OptiMAL-IT' (Cressier, Switzerland) rapid antigen tests were examined in parallel with routine microscopy for a select population of high risk individuals: 202 pregnant women and 200 children less than 5 years old in an endemic setting in Ghana. Results of both diagnostic methods were compared to that of cross-checking microscopy, taken as gold standard, at the Navrongo Health Research Centre. Of the 402 patients, 218 (54.2%) were confirmed with Plasmodium falciparum infections by cross-checking. All 218 patients (100%) were accurately diagnosed with malaria by routine microscopy. Of these, 151 (69.3%) were positive by DiaMed OptiMAL-IT test (26 false positives, 67 false negatives). DiaMed OptiMAL-IT had the following performance indicators for detection of P. falciparum among pregnant women and children less than 5 years respectively: Sensitivity-50.5% [95% CI (40.6-60.3)], 87.7% [95% CI (78.7-92.1)]; Specificity-82.5% [95% CI (73.1-89.1)], 89.6% [95% CI (80.8-94.8)]; Predictive values for positive tests-75.7% [95% CI (63.7-84.8)], 91.6% [95% CI(85.2-95.8%)]; Predictive values for negative tests-60.6% [95% CI (51.7-68.9)], 83.8% [95% CI (74.5-90.3)]; Likelihood ratio for positive tests-2.88, 10.8; Likelihood ratio for negative tests-0.59, 0.19; Cohens Kappa values-0.33 [95% CI (0.20-0.43), 0.76 [95% CI (0.65-0.83)]. Our results suggest that DiaMed OptiMAL-IT tests should not replace microscopy in our endemic setting.