- Objective The objective was to investigate obstetric risk factors, complications, and outcomes of pregnancies complicated by moderate to severe thrombocytopenia. Materials and methods A retrospective case-control study comparing 199 pregnant women with moderate to severe thrombocytopenia (platelet count below 100 × 109/l) with 201 pregnant women without thrombocytopenia, who delivered between January 2003 to April 2004. Stratified analysis, using the Mantel–Haenszel procedure was performed in order to control for confounders. Results The main causes of thrombocytopenia were gestational thrombocytopenia (GT) (59.3%), immune thrombocytopenic purpura (ITP) (11.05%), preeclampsia (10.05%), and HELLP (Hemolysis, elevated liver enzymes and low platelet count) syndrome (12.06%). Women with thrombocytopenia were significantly older (30.7 ± 5.9 versus 28.7 ± 5.7; p = 0.001) compared with patients without thrombocytopenia, and had higher rates of labor induction (OR = 4.0, 95% CI = 2.2–7.6, p < 0.001) and preterm deliveries (OR = 3.5, 95% CI = 1.9–6.5, p < 0.001). Even after controlling for labor induction, using the Mantel–Haenszel technique, thrombocytopenia was significantly associated with preterm delivery (weighted OR = 3.14, 95% CI = 1.7–6.0, p < 0.001). Higher rates of placental abruption were found in pregnant women with thrombocytopenia (OR = 6.2, 95% CI = 1.7–33.2, p = 0.001). In a comparison of perinatal outcomes, higher rates of Apgar scores <7 at 5 min were noted in infants of mothers with thrombocytopenia (OR = 6.3, 95% CI = 1.8–33.8, p = 0.001), intrauterine growth restriction (IUGR; OR = 4.6, 95% CI = 1.5–19.1, p = 0.003), and stillbirth (65/1000 versus 0 p < 0.001). These adverse perinatal outcomes were found in rare causes of thrombocytopenia such as disseminated intravascular coagulation (DIC), familial thrombotic thrombocytopenic purpura (TTP), anti-phospholipid antibodies (APLA) syndrome, and myeloproliferative disease, and not among patients with GT. Conclusions Moderate to severe maternal thrombocytopenia points to a higher degree of severity of the primary disease, which increases perinatal complications. However, the adverse outcome is specifically attributed to preeclampsia, HELLP syndrome, and rare causes, while the perinatal outcome of GT and ITP is basically favorable. Special attention should be given to patients with thrombocytopenia due to preeclampsia, HELLP syndrome, and rarer causes during pregnancy.