Malaria continues to be a major public health problem in Al-Hodeidah G. A cross-sectional malariometic parasitic survey including 4000 Yemenis of various age /sex groups were enrolled in this study from 43 villages/or Harah in five selected districts representing Al-Hodeidah G. Duplicate thin and thick blood smears were stained with Giemsa's stain and examined. Out of 4000 examined slides, 646 (16.2%) were found to be malaria positive, 508 (78.6%) of them were detected through ACD, while 138 (21.4%) cases were detected by PCD. The overall parasite rate was 16.2%, a situation of prevalently mesoendemic condition. P. falciparum was the predominant species recorded (96.7%), followed by P. vivax (1.7%), the least prevalent was P. malariae (0.3%). Yemen has been considered free of ovale malaria. The recorded an indigenous case of P. ovale for the first time in Yemen should be taken into consideration for the existence of this particular Plasmodium species when surveying for malaria in the future. The present study was the first document in Yemen to compare simultaneously the in vivo and in vitro response to chloroquine among 209 of P. falciparum field isolate patients that were satisfied all criteria of WHO for the implementation of the in vivo and in vitro tests and were obtained by PCD and ACD methods. Chloroquine resistance of local strain of P. falciparum was recorded in all studied districts (Zabid, Bajil, Azohrah, Azaidiah and Al-Hodeidah city). RIII (high level of resistance) was recorded for the first time in Yemen and should be taken into consideration in the treatment of infected malaria patients. This calls for urgent revision of the current malaria treatment policy in Yemen where chloroquine is the first-line treatment of uncomplicated P. falciparum malaria.