Spontaneous coronary artery dissection (SCAD) is a common cause of pregnancy-associated myocardial infarction. This study compares the clinical course and longitudinal follow-up of 22 cases of pregnancy-associated SCAD (P-SCAD) with 285 cases of non-pregnancy SCAD (NP-SCAD) from Kaiser Permanente Northern California between September 2002 through June 2017. Age in the P-SCAD group was significantly lower than in the NP-SCAD group (37.1 ± 5.7 years vs 50.9 ± 9.9 years, respectively; P<.001). Both cohorts were racially diverse, but the P-SCAD group had fewer whites (27.3% vs 50.7%; P=.03). The P-SCAD group had higher multigravidity (54.6% vs 31.4%; P=.03) and 68.2% were of advanced maternal age. The rates of ST-elevation myocardial infarction, ventricular tachycardia/fibrillation, and left main coronary dissection were similar. Proximal vessel dissection (31.8% vs 7.7%; P<.01), multiple vessel dissection (31.8% vs 9.5%; P<.01), and reduced ejection fraction at presentation (49.6 ± 10.5% vs 55.7 ± 10.4%; P=.01) were more common in the P-SCAD group vs the NP-SCAD group, respectively. More P-SCAD patients had cardiogenic shock and/or required intra-aortic balloon pump support (9.1% vs 1.1%; P=.04). Medical management was the principal coronary treatment strategy in both groups. P-SCAD patients experienced more major adverse cardiovascular events (50.0% vs 26.0%; P=.02), driven by persistent reduced ejection fraction ≤45% at follow-up (18.2% vs 5.3%; P=.04). Recurrent SCAD (18.2% vs 11.2%; P=.31) and cardiovascular death (0% vs 0.4%; P>.99) were similar in the P-SCAD group vs the NP-SCAD group, respectively. Seven patients had successful subsequent pregnancies without cardiac complications. P-SCAD has a higher-risk presentation, but similar long-term prognosis compared with NP-SCAD. In addition, subsequent pregnancy after SCAD may present acceptable risk.